12,269 results on '"Androstenedione"'
Search Results
102. Androgens by immunoassay and mass spectrometry in children with 46,XY disorder of sex development
- Author
-
Letícia Ribeiro Oliveira, Carlos Alberto Longui, Guilherme Guaragna-Filho, José Luiz Costa, Rafael Lanaro, David Antônio Silva, Maria Izabel Chiamolera, Maricilda Palandi de Mello, André Moreno Morcillo, Andrea Trevas Maciel-Guerra, and Gil Guerra-Junior
- Subjects
testosterone ,testicles ,androstenedione ,androgen insensitivity syndrome ,5α-reductase ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Objective: Steroid measurement is a challenge in pediatric endocrinology. Currently, liquid chromatography with tandem mass spectrometry (LC-MS/MS) is considered a gold standard for this purpose. The aim of this study was to co mpare both LC-MS/MS and immunoassay (IA) for androgens before and after human recom binant chorionic gonadotropin (rhCG) stimulus in children with 46,XY disorders o f sex development (DSD). Methods: Nineteen patients with 46,XY DSD were evaluated; all of them w ere prepubertal and non-gonadectomized. Testosterone, dihydrotestosterone (DHT), DHEA and androstenedione were measured by IA and LC-MS/MS before and 7 d ays after rhCG injection. The correlation between IA and LC-MS/MS was analyzed by the intraclass correlation coefficient (ICC) and Spearman’s rank correlation coe fficient (SCC). For concordance analysis the Passing and Bablok (PB) regression and the Bland and Altman (BA) method were used. Results: Testosterone showed excellent correlation (ICC = 0.960 and SCC = 0.964); DHT showed insignificant and moderate correlations as indicated by I CC (0.222) and SCC (0.631), respectively; DHEA showed moderate correlation (ICC = 0.585 and SCC = 0.716); and androstenedione had poor and moderate correlations in ICC ( 0.363) and SCC (0.735), respectively. Using the PB method, all hormones showed a linear correlation, but proportional and systematic concordance errors were detected fo r androstenedione, systematic errors for testosterone and no errors for DHEA and D HT. By the BA method, there was a trend of IA to overestimate testosterone and andros tenedione and underestimate DHEA and DHT when compared to LC-MS/MS. Conclusion: Traditional IA should be replaced by LC-MS/MS for the androgen s measurement in prepubertal children whenever is possible.
- Published
- 2020
- Full Text
- View/download PDF
103. A Model for Predicting Polycystic Ovary Syndrome Using Serum AMH, Menstrual Cycle Length, Body Mass Index and Serum Androstenedione in Chinese Reproductive Aged Population: A Retrospective Cohort Study
- Author
-
Huiyu Xu, Guoshuang Feng, Kannan Alpadi, Yong Han, Rui Yang, Lixue Chen, Rong Li, and Jie Qiao
- Subjects
PCOS ,website-based tool ,AMH ,menstrual cycle length ,BMI ,androstenedione ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
BackgroundA clinical diagnosis of polycystic ovary syndrome (PCOS) can be tedious with many different required tests and examinations. Furthermore, women with PCOS have increased risks for several metabolic complications, which need long-term health management. Therefore, we attempted to establish an easily applicable model to identify such women at an early stage.ObjectiveTo develop an easy-to-use tool for screening PCOS based on medical records from a large assisted reproductive technology (ART) center in China.Materials and MethodsA retrospective observational cohort from Peking University Third Hospital was used in the study. Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression with 10-fold cross-validation was applied to construct the model. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity values were used to evaluate and compare the models.Design, Setting, and ParticipantsThis retrospective cohort study included 21,219 ovarian stimulation cycle records from January to December 2019 in Peking University Third Hospital.Main Outcomes and MeasuresThe main outcome was whether there was a clinical diagnosis of PCOS. The independent variables included were age, body mass index (BMI), upper limit of menstrual cycle length (UML), basal serum levels of anti-Müllerian hormone (AMH), testosterone androstenedione, antral follicle counts et al.ResultsWe have established a new mathematical model for diagnosing PCOS using serum AMH and androstenedione levels, UML, and BMI, with AUC values of 0.855 (0.838–0.870), 0.848 (0.791–0.891), 0.846 (0.812–0.875) in the training, validation, and testing sets, respectively. The contribution of each predictor to this model were: AMH 41.2%; UML 35.2%; BMI 4.3%; and androstenedione 3.7%. The top 10 groups of women most predicted to develop PCOS were demonstrated. An online tool (http://121.43.113.123:8888/) has been developed to assist Chinese ART clinics.ConclusionsThe models and online tool we established here might be helpful for screening and identifying women with undiagnosed PCOS in Asian populations and could assist in the long-term management of related metabolic disorders.
- Published
- 2022
- Full Text
- View/download PDF
104. Histological evaluation of sex differentiation and early sex identification in hatchery-produced greater amberjack (Seriola dumerili) reared in sea cages.
- Author
-
Papadaki, Maria, Mandalakis, Manolis, Anastasiou, Thekla I., Pouli, Marina, Asderis, Michalis, Katharios, Pantelis, Papandroulakis, Nikos, and Mylonas, Constantinos C.
- Abstract
The histological process of gonadal differentiation, together with the endocrine changes of sex steroid hormones and some of their precursors, was studied in hatchery-produced greater amberjack Seriola dumerili from 101 until 408 days post-hatching (dph), with samplings conducted every 50 days. Histological processing showed that sex differentiation began at 101 dph with the formation of the ovarian cavity in females, while the presumptive males did not yet contain any germ cells in their gonad. At 150 dph, we observed the first germ cells in the developing testes. Sex differentiation in almost all sampled individuals was complete at 408 dph. No size dimorphism was observed between the sexes, and the sex ratio was 1:1, suggesting that there was no influence of early rearing in captivity on sex differentiation. Plasma concentrations of adrenosterone (Ad), androstenedione (Δ4), 11-ketotestosterone (11ΚΤ), testosterone (Τ), estradiol (Ε
2 ), progesterone (P4) and 17,20β-dihydroxy-4-pregnen-3-one (17,20βP) were measured in males and females with the use of liquid chromatography tandem mass spectrometry (LC–MS/MS) to examine their role in the sex differentiation process. From the seven hormones, the only one that exhibited differences between the sexes was 11-KT and the plasma 11-KT concentration was found to be a useful indication of greater amberjack sex. Variations were observed in the mean values of Ad, Δ4, 11-KT, T, P4 and 17,20βP over time in one or both sexes, indicating their involvement in the sex differentiation process. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
105. Associations of serum androgens with coronary heart disease and interaction with age: The Henan Rural Cohort Study.
- Author
-
Liu, Pengling, Liu, Xue, Wei, Dandan, Nie, Luting, Fan, Keliang, Zhang, Li, Wang, Lulu, Liu, Xiaotian, Hou, Jian, Yu, Songcheng, Li, Linlin, Wang, Chongjian, Huo, Wenqian, and Mao, Zhenxing
- Abstract
Background and Aims: We aimed to investigate the associations of testosterone and androstenedione with coronary heart disease, and the interaction effect of testosterone or androstenedione and age on coronary heart disease.Methods and Results: A total of 6178 participants were included in this study. Serum testosterone and androstenedione were detected by liquid chromatography-tandem mass spectrometry. Logistic regression and restricted cubic splines were used to assess the independent effects of testosterone and androstenedione on coronary heart disease. Interactive plots were employed to examine the interaction effects of testosterone or androstenedione with age on coronary heart disease. After adjusting for multiple variables, serum testosterone and androstenedione levels were negatively associated with coronary heart disease in males (tertile 3 vs tertile 1, odd ratio (OR) = 0.56, 95% confidence interval (CI) (0.33, 0.96), and OR = 0.40, 95% CI (0.22, 0.74)). Per 1 unit increase in ln-testosterone and ln-androstenedione was associated with a 24% (OR = 0.76, 95% CI (0.63, 0.91)) and 30% (OR = 0.69, 95% CI (0.55, 0.86)) lower risk of coronary heart disease, respectively. Additionally, the positive association of age with coronary heart disease was attenuated by increasing concentrations of ln-testosterone and ln-androstenedione concentration in males.Conclusions: The results indicated that serum testosterone and androstenedione were negatively associated with coronary heart disease risk in Chinese rural males. To some extent, this study supports the application of hormone therapy in males with coronary heart disease, which can contribute to reducing the burden of coronary heart disease and related cardiovascular disease. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
106. Testosterone and androstenedione are positively associated with anti‐Müllerian hormone in premenopausal women.
- Author
-
Islam, Rakibul M., Bell, Robin J., Skiba, Marina A., and Davis, Susan R.
- Subjects
- *
ANTI-Mullerian hormone , *LIQUID chromatography-mass spectrometry , *ANDROSTENEDIONE , *TESTOSTERONE , *POLYCYSTIC ovary syndrome - Abstract
Objective: To document associations between anti‐Müllerian hormone (AMH) and circulating androgens in nonhealthcare‐seeking premenopausal women. Design: Community‐based, cross‐sectional study. Setting: Eastern states of Australia. Participants: Women aged 18–39 years not using systemic hormones, not pregnant or breastfeeding within 3 months, and not postmenopausal. Measurements: AMH, measured by the Beckman Access 2, 2 site immunometric assay from fresh samples, and testosterone, androstenedione, dehydroepiandrosterone (DHEA) and 11‐oxygenated C19 steroids, measured by liquid chromatography–tandem mass spectrometry. Results: Data were available for 794 women, median age of 33 years (range: 18–39). 76.1% were of European ancestry and 48.2% were parous. Serum AMH was positively associated with testosterone (rho =.29, p <.001) androstenedione (rho =.39, p <.001) and DHEA (rho =.10, p =.005) but not 11‐ketoandrostenedione or 11‐ketotestosterone. When adjusted for age, body mass index and smoking, using quantile regression, independent positive associations remained between AMH and testosterone (β coefficient: 20.90, 95% confidence interval [CI]: 13.79–28.03; p <.001) and androstenedione (β coefficient: 5.90, 95% CI: 3.76–8.03; p <.001). The serum concentration of testosterone was greater at the top AMH quintile than other quintiles (0.56 nmol/L [range: 0.21–1.90] vs. 0.36 nmol/L [range: 0.13–0.87]; p =.001) in women with self‐reported polycystic ovary syndrome. Conclusions: The positive associations between serum testosterone and androstenedione and AMH in premenopausal women is consistent with androgens directly or indirectly influencing AMH production during follicular development. As the highest AMH concentrations are most likely to be seen in women with multifollicular ovaries, it would be expected that women with multifollicular ovaries would have higher serum testosterone. Therefore, whether hyperandrogenemia and multifollicular ovaries should be considered independent characteristics of polycystic ovary syndrome warrants review. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
107. Adrenal androgen trajectories are established during childhood in preterm boys.
- Author
-
Kvernebo Sunnergren, Kjersti, Karlsson, Ann‐Katrine, Allvin, Kerstin, Nilsson, Staffan, Ankarberg‐Lindgren, Carina, Dahlgren, Jovanna, Karlsson, Ann-Katrine, and Ankarberg-Lindgren, Carina
- Subjects
- *
LIQUID chromatography-mass spectrometry , *BIRTH size , *ANDROGENS , *GESTATIONAL age , *ANTHROPOMETRY , *DEHYDROEPIANDROSTERONE , *RESEARCH funding , *ANDROSTENEDIONE , *LONGITUDINAL method - Abstract
Aim: We investigated longitudinal adrenal androgen concentrations and any relationship between gestational age, birth size, anthropometric parameters and adrenal androgen concentrations during childhood in boys born moderate to late preterm.Methods: This longitudinal, prospective study included 58 boys born at 32+0 to 36+6 weeks of gestation. Dehydroepiandrosterone sulphate and androstenedione were analysed by liquid chromatography-tandem mass spectrometry, and anthropometric data were recorded from 5 to 10 years of age.Results: Dehydroepiandrosterone sulphate concentrations correlated with weight standard deviations scores (SDS) from 7 to 10 years of age and waist-to-height ratios at seven and 10 years of age. Androstenedione correlated with weight SDS from 7 to 10 years of age and waist-to-height ratios at 10 years of age. Longitudinal analysis showed a relationship between weight SDS and waist-to-height SDS and dehydroepiandrosterone sulphate (p < 0.001 and p < 0.001, respectively) and androstenedione (p = 0.002 and p = 0.003, respectively), independently of age.Conclusion: The trajectories of anthropometric parameters and adrenal androgen secretion were consistent from 5 to 10 years of age in this cohort. The body composition reflected by current weight and the waist-to-height ratio, rather than gestational age and birth size, was associated with adrenal androgen secretion. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
108. Tildacerfont in Adults With Classic Congenital Adrenal Hyperplasia: Results from Two Phase 2 Studies.
- Author
-
Sarafoglou, Kyriakie, Barnes, Chris N., Huang, Michael, Imel, Erik A., Madu, Ivy-Joan, Merke, Deborah P., Moriarty, David, Nakhle, Samer, Newfield, Ron S., Vogiatzi, Maria G., and Auchus, Richard J.
- Subjects
ADRENOGENITAL syndrome ,GLUCOCORTICOIDS ,ADRENOCORTICOTROPIC hormone ,ADRENAL diseases ,RESEARCH ,PROGESTERONE ,RESEARCH methodology ,CELL receptors ,MEDICAL cooperation ,EVALUATION research ,COMPARATIVE studies ,GLASGOW Coma Scale ,RESEARCH funding ,ANDROSTENEDIONE ,LONGITUDINAL method - Abstract
Context: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) is typically treated with lifelong supraphysiologic doses of glucocorticoids (GCs). Tildacerfont, a corticotropin-releasing factor type-1 receptor antagonist, may reduce excess androgen production, allowing for GC dose reduction.Objective: Assess tildacerfont safety and efficacy.Design and Setting: Two Phase 2 open-label studies.Patients: Adults with 21OHD.Intervention: Oral tildacerfont 200 to 1000 mg once daily (QD) (n = 10) or 100 to 200 mg twice daily (n = 9 and 7) for 2 weeks (Study 1), and 400 mg QD (n = 11) for 12 weeks (Study 2).Main Outcome Measure: Efficacy was evaluated by changes from baseline at 8 am in adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), and androstenedione (A4) according to baseline A4 ≤ 2× upper limit of normal (ULN) or A4 > 2× ULN. Safety was evaluated using adverse events (AEs) and laboratory assessments.Results: In Study 1, evaluable participants with baseline A4 > 2× ULN (n = 11; 19-67 years, 55% female) had reductions from baseline in ACTH (-59.4% to -28.4%), 17-OHP (-38.3% to 0.3%), and A4 (-24.2% to -18.1%), with no clear dose response. In Study 2, participants with baseline A4 > 2× ULN (n = 5; 26-63 years, 40% female) had ~80% maximum mean reductions in biomarker levels. ACTH and A4 were normalized for 60% and 40%, respectively. In both studies, participants with baseline A4 ≤ 2× ULN maintained biomarker levels. AEs (in 53.6% of patients overall) included headache (7.1%) and upper respiratory tract infection (7.1%).Conclusions: For patients with 21OHD, up to 12 weeks of oral tildacerfont reduced or maintained key hormone biomarkers toward normal. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
109. Serum Testosterone to Androstenedione Ratio Predicts Metabolic Health in Normal-Weight Polycystic Ovary Syndrome Women.
- Author
-
Dumesic, Daniel A, Tulberg, Ayli, McNamara, Megan, Grogan, Tristan R, Abbott, David H, Naik, Rajanigandha, Lu, Gwyneth, and Chazenbalk, Gregorio D
- Subjects
POLYCYSTIC ovary syndrome ,TYPE 2 diabetes ,DUAL-energy X-ray absorptiometry ,ANDROSTENEDIONE ,GLUCOSE tolerance tests ,TESTOSTERONE - Abstract
Context Increased aldo-keto reductase 1C3 (AKR1C3)-mediated conversion of androstenedione (A4) to testosterone (T) promotes lipid storage in subcutaneous (SC) abdominal adipose in overweight/obese polycystic ovary syndrome (PCOS) women. Objective This work examines whether an elevated serum T/A4 ratio, as a marker of enhanced AKR1C3 activity in SC abdominal adipose, predicts metabolic function in normal-weight PCOS women. Methods This prospective cohort study took place in an academic center and comprised 19 normal-weight PCOS women and 21 age- and body mass index–matched controls. Interventions included circulating hormone/metabolic determinations, intravenous glucose tolerance testing, total body dual-energy x-ray absorptiometry, and SC abdominal fat biopsy. Serum T/A4 ratios, hormone/metabolic measures, and AKR1C3 expression of adipocytes matured in vitro were compared between female types; serum T/A4 ratios were correlated with serum lipids, adipose insulin resistance (adipose-IR), homeostatic model assessment of insulin resistance (HOMA-IR) and insulin sensitivity (Si). Results Increased serum T/A4 ratios (P = .040) and log adipose-IR values (P = .002) in PCOS women vs controls were accompanied by AKR1C3 messenger RNA overexpression of PCOS adipocytes matured in vitro (P = .016). Serum T/A4 ratios in PCOS women, but not controls, negatively correlated with log triglycerides (TGs: R = –0.65, P = .002) and the TG index (R = –0.57, P = .011). Adjusting for serum free T, serum T/A4 ratios in PCOS women remained negatively correlated with log TG (R = –0.57, P = .013) and TG index (R = –0.50, P = .036), respectively, without significant relationships with other metabolic measures. Conclusion An elevated serum T/A4 ratio, as a marker of enhanced AKR1C3 activity in SC abdominal adipose, predicts healthy metabolic function in normal-weight PCOS women. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
110. Sex hormones in female residents of Yamal-Nenets autonomous district depending on the fertility status
- Author
-
A. E. Elfimova
- Subjects
sex hormones ,androstenedione ,dihydrotestosterone ,estrone ,sex hormone-binding globulin ,women ,reproductive age ,postmenopause ,north ,Medicine - Abstract
Severe climatic conditions adversely affect the human reproductive function; there is evidence of earlier aging of the endocrine system in residents of the northern territories. However, there is insufficient data on the content of androgens and estrogens in postmenopausal women of the North. This determined the aim of the work - to study the characteristics of the content of sex hormones in fertile and postmenopausal women in the Arctic zone of the Russian Federation. Material and methods. In the period of increasing daylight hours, there were examined 60 residents of the Yamal-Nenets Autonomous District of the reproductive (n = 33) and postmenopausal (n = 27) periods. The serum luteinizing, follicle-stimulating hormones, progesterone, dehydroepiandrosterone sulfate, dihydrotestosterone, androstenedione, total and free fractions of testosterone, estrogen, estrone, sex-hormone-binding globulin were determined by immunoassay analysis using sets of «Khema-Medica» (Russia), Alkor-Bio (Russia), DRG (Germany). The research results were statistically processed using application software package STATISTIC 10.0. Results. There were shown high median values of progesterone (2.41 nmol/L) and dihydrotestosterone (191.02 pg/ml) in postmenopausal women, as well as increased concentrations of sex-hormone-binding globulin in both fertile (170.66 nmol/L) and postmenopausal (154.84 nmol/L) women. At the same time, free testosterone levels are slightly reduced, especially in postmenopausal women (0.50 pg/ml). Conclusion. The revealed features of the hormonal profile of women living in high latitudes may be an unfavorable factor for the development of various metabolic disorders.
- Published
- 2020
- Full Text
- View/download PDF
111. Androgen-associated and androgen-independent causes of alopecia and acne in women. Literature reviewgen-associated and androgen-independent causes of alopecia and acne in women. Literature review
- Author
-
І. В. Сідорова, Т. М. Тутченко, О. А. Бурка, Л. М. Семенюк, I. Г. Ноговська, and Л. В. Дем’яненко
- Subjects
androgens ,testosterone ,androstenedione ,dihydrotestosterone ,alopecia ,androgenetic alopecia ,telogen effluvium ,acne ,antimicrobial resistance ,Gynecology and obstetrics ,RG1-991 - Abstract
This article refers to the issues of alopecia and acne pathogenesis: anatomy of hair and sebaceous glands, biological factors affecting the stages of hair development and function of sebaceous glands. Alopecia is divided into two large groups: scaring and non-scaring alopecia, the later is represented by alopecia areata, telogen effluvium, and female pattern hair loss/androgenetic alopecia (FPHL/AGA). Before starting the search for systemic causes it is necessary to predetermine the type of alopecia on the basis of medical history and external manifestations. FPHL /AGA as a most common form of alopecia can often coexist with another common pathology – telogen effluvium, this fact determines therapeutic approaches and their results. Main pathogenetic mechanisms, approaches to differential diagnostics and treatment of the main specified types of non-scarring alopecia are reviewed. FPHL/AGA is a main type of alopecia which is often referred to gynecologists/endocrinologists. It is now regarded a multifactorial pathology with the involvement of a genetic component, androgen receptor gene expression, dihydrotestosterone synthesis and local low grade inflammation specifics. FPHL/AGA can be with and without hyperandrogenism, in both cases it can be accompanied by an increased risk of metabolic syndrome. In case of FPHL/AGA with hyperandrogenism the success of treatment depends on the consistent coordinated work of gynecologist/endocrinologist and dermatologist/trichologist, which allows combining systemic and local therapy in a timely manner. Also contemporary views on the acne pathogenesis are reviewed. Given the complex nature of acne its therapy is also complex and stepwise. According to current clinical guidelines and recent studies of the microbial component of acne pathogenesis the following conclusions are formulated. Patients with acne require assessment of androgen status, determination of the hyperandrogenism source, including evaluation of tissue androgens; phenotype of the syndrome and cardio-metabolic risks should be determined in patients with polycystic ovary syndrome; it is advisable to determine antimicrobial susceptibility of pathogens isolated from the inflamed pilosebaceous unit if acne form requires the local or systemic antibacterial therapy.
- Published
- 2020
- Full Text
- View/download PDF
112. Androstenedione as a potential predictor of ovarian response in assisted reproductive technology programs
- Author
-
Anna G. Burduli, Natalia A. Kitsilovskaya, Yuliya V. Sukhova, Irina A. Vedikhina, Tatiana Yu. Ivanets, Vitaliy V. Chagovets, Nataliia L. Starodubtseva, and Vladimir E. Frankevich
- Subjects
ovarian response ,assisted reproductive technology program ,follicular fluid ,steroid hormones ,androstenedione ,high-performance liquid chromatography-mass spectrometry ,chemiluminescent immunoassay ,Gynecology and obstetrics ,RG1-991 - Abstract
Aim. To assess the possibility of using androstenedione levels in blood serum and follicular fluid to predict ovarian response in assisted reproductive technology programs and to conduct a comparative analysis of the results obtained by 2 methods chemiluminescent immunoassay (CLIA) and high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS). Materials and methods. A prospective study included 55 couples who received in vitro fertilization/intracytoplasmic sperm injection and embryo transfer program therapy. The patients were divided into 3 groups depending on the ovarian response to stimulation: 1st (13 oocytes, n=4), 2nd (49 oocytes, n=27), 3rd (over 10 oocytes, n=24). Androstenedione levels were measured in blood serum obtained on the day of transvaginal ovarian puncture and in follicular fluid samples with CLIA and HPLC-MS/ MS methods at the laboratories of Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology. Results. On the day of transvaginal ovarian puncture, the serum androstenedione levels, which were measured by HPLC-MS/MS, were increasing with an increase of the number of oocytes obtained. The CLIA method revealed a difference in the androstenedione levels between the groups with the number of oocytes obtained of less than 3 and more than 10. Moreover, the androstenedione levels measured by CLIA were significantly different between the patient groups (p0.05). Comparison of serum androstenedione levels measured by CLIA and HPLC-MS/MS, showed high correlations between the values [=0.73 (p0.001)], which makes it possible to use both methods equally, given the existing equipment of the clinical base. Conclusion. Prediction of ovarian response to stimulation is an important step in assisted reproductive technology programs. Measuring androstenedione concentration in blood serum on the day of transvaginal ovarian puncture with highly specific methods (CLIA and HPLC-MS/MS) can be used to predict the degree of ovarian response along with the traditional assessment of the ovarian reserve based on determining anti-Mullerian hormone levels in the early follicular phase of the menstrual cycle.
- Published
- 2020
- Full Text
- View/download PDF
113. Improving phytosterol biotransformation at low nitrogen levels by enhancing the methylcitrate cycle with transcriptional regulators PrpR and GlnR of Mycobacterium neoaurum
- Author
-
Yang Zhang, Xiuling Zhou, Xuemei Wang, Lu Wang, Menglei Xia, Jianmei Luo, Yanbing Shen, and Min Wang
- Subjects
Mycobacterium neoaurum ,Androstenedione ,Methylcitrate cycle ,Transcriptional regulator ,Nitrogen level ,Microbiology ,QR1-502 - Abstract
Abstract Background Androstenedione (AD) is an important steroid medicine intermediate that is obtained via the degradation of phytosterols by mycobacteria. The production process of AD is mainly the degradation of the phytosterol aliphatic side chain, which is accompanied by the production of propionyl CoA. Excessive accumulation of intracellular propionyl-CoA produces a toxic effect in mycobacteria, which restricts the improvement of production efficiency. The 2-methylcitrate cycle pathway (MCC) plays a significant role in the detoxification of propionyl-CoA in bacterial. The effect of the MCC on phytosterol biotransformation in mycobacteria has not been elucidated in detail. Meanwhile, reducing fermentation cost has always been an important issue to be solved in the optimizing of the bioprocess. Results There is a complete MCC in Mycobacterium neoaurum (MNR), prpC, prpD and prpB in the prp operon encode methylcitrate synthase, methylcitrate dehydratase and methylisocitrate lyase involved in MCC, and PrpR is a specific transcriptional activator of prp operon. After the overexpression of prpDCB and prpR in MNR, the significantly improved transcription levels of prpC, prpD and prpB were observed. The highest conversion ratios of AD obtained by MNR-prpDBC and MNR-prpR increased from 72.3 ± 2.5% to 82.2 ± 2.2% and 90.6 ± 2.6%, respectively. Through enhanced the PrpR of MNR, the in intracellular propionyl-CoA levels decreased by 43 ± 3%, and the cell viability improved by 22 ± 1% compared to MNR at 96 h. The nitrogen transcription regulator GlnR repressed prp operon transcription in a nitrogen-limited medium. The glnR deletion enhanced the transcription level of prpDBC and the biotransformation ability of MNR. MNR-prpR/ΔglnR was constructed by the overexpression of prpR in the glnR-deleted strain showed adaptability to low nitrogen. The highest AD conversion ratio by MNR-prpR/ΔglnR was 92.8 ± 2.7% at low nitrogen level, which was 1.4 times higher than that of MNR. Conclusion Improvement in phytosterol biotransformation after the enhancement of propionyl-CoA metabolism through the combined modifications of the prp operon and glnR of mycobacteria was investigated for the first time. The overexpress of prpR in MNR can increase the transcription of essential genes (prpC, prpD and prpB) of MCC, reduce the intracellular propionyl-CoA level and improve bacterial viability. The knockout of glnR can enhance the adaptability of MNR to the nitrogen source. In the MNRΔglnR strain, overexpress of prpR can achieve efficient production of AD at low nitrogen levels, thus reducing the production cost. This strategy provides a reference for the economic and effective production of other valuable steroid metabolites from phytosterol in the pharmaceutical industry.
- Published
- 2020
- Full Text
- View/download PDF
114. Of 11 candidate steroids, corticosterone concentration standardized for mass is the most reliable steroid biomarker of nutritional stress across different feather types
- Author
-
Alexis Will, Katherine Wynne‐Edwards, Ruokun Zhou, and Alexander Kitaysky
- Subjects
17‐hydroxyprogesterone ,androstenedione ,corticosterone ,cortisol ,cortisone ,feather ,Ecology ,QH540-549.5 - Abstract
Abstract Measuring corticosterone in feathers has become an informative tool in avian ecology, enabling researchers to investigate carry‐over effects and responses to environmental variability. Few studies have, however, explored whether corticosterone is the only hormone expressed in feathers and is the most indicative of environmental stress. Essential questions remain as to how to compare hormone concentrations across different types of feathers and whether preening adds steroids, applied after feather growth. We used liquid chromatography coupled to tandem mass spectrometry to quantify a suite of 11 steroid hormones in back, breast, tail, and primary feathers naturally grown at overlapping time intervals by rhinoceros auklet Cerorhinca monocerata captive‐reared fledglings and wild‐caught juveniles. The captive‐reared birds were raised on either a restricted or control diet. Measured steroids included intermediates in the adrenal steroidogenesis pathway to glucocorticoids and the sex steroids pathway to androgens and estrogens. Corticosterone was detected in the majority of feathers of each type. We also detected cortisone in back feathers, androstenedione in breast feathers, and testosterone in primary feathers. Captive fledglings raised on a restricted diet had higher concentrations of corticosterone in all four feather types than captive fledglings raised on a control diet. Corticosterone concentrations were reliably repeatable across feather types when standardized for feather mass, but not for feather length. Of the seven hormones looked for in uropygial gland secretions, only corticosterone was detected in one out of 23 samples. We conclude that corticosterone is the best feather‐steroid biomarker for detection of developmental nutritional stress, as it was the only hormone to manifest a signal of nutritional stress, and that exposure to stress can be compared among different feather types when corticosterone concentrations are standardized by feather mass.
- Published
- 2019
- Full Text
- View/download PDF
115. Glutathione Transferases as Efficient Ketosteroid Isomerases
- Author
-
Bengt Mannervik, Aram Ismail, Helena Lindström, Birgitta Sjödin, and Nancy H. Ing
- Subjects
ketosteroid isomerase ,androstenedione ,progesterone ,ecdysteroid ,glutathione ,steroid hormone ,Biology (General) ,QH301-705.5 - Abstract
In addition to their well-established role in detoxication, glutathione transferases (GSTs) have other biological functions. We are focusing on the ketosteroid isomerase activity, which appears to contribute to steroid hormone biosynthesis in mammalian tissues. A highly efficient GST A3-3 is present in some, but not all, mammals. The alpha class enzyme GST A3-3 in humans and the horse shows the highest catalytic efficiency with kcat/Km values of approximately 107 M−1s−1, ranking close to the most active enzymes known. The expression of GST A3-3 in steroidogenic tissues suggests that the enzyme has evolved to support the activity of 3β-hydroxysteroid dehydrogenase, which catalyzes the formation of 5-androsten-3,17-dione and 5-pregnen-3,20-dione that are substrates for the double-bond isomerization catalyzed by GST A3-3. The dehydrogenase also catalyzes the isomerization, but its kcat of approximately 1 s−1 is 200-fold lower than the kcat values of human and equine GST A3-3. Inhibition of GST A3-3 in progesterone-producing human cells suppress the formation of the hormone. Glutathione serves as a coenzyme contributing a thiolate as a base in the isomerase mechanism, which also involves the active-site Tyr9 and Arg15. These conserved residues are necessary but not sufficient for the ketosteroid isomerase activity. A proper assortment of H-site residues is crucial to efficient catalysis by forming the cavity binding the hydrophobic substrate. It remains to elucidate why some mammals, such as rats and mice, lack GSTs with the prominent ketosteroid isomerase activity found in certain other species. Remarkably, the fruit fly Drosophila melanogaster, expresses a GSTE14 with notable steroid isomerase activity, even though Ser14 has evolved as the active-site residue corresponding to Tyr9 in the mammalian alpha class.
- Published
- 2021
- Full Text
- View/download PDF
116. Exposure of adult zebrafish to androstenedione alters thyroid hormone levels and the transcriptional expression of genes related to the hypothalamus-pituitary-thyroid axis
- Author
-
Yan-Qiu Liang, Yanjie Situ, Linchun Xie, Jialiang Huo, Zhongdian Dong, Chengyong Li, and Zhong Lin
- Subjects
Androstenedione ,Thyroid hormones ,Hypothalamus-pituitary-thyroid axis ,Zebrafish ,Androgen ,Aquaculture. Fisheries. Angling ,SH1-691 - Abstract
Androstenedione (AED) is a naturally occurring androgen that is released into the environment through human and animal excretion. Several studies have shown that AED can interfere with the normal growth, development, and reproduction of organisms. However, studies examining the thyroid system, an important part of endocrine system of fish, are still lacking. This study examines thyroid hormone levels including T3 and T4, and transcriptional expression levels of genes associated with the hypothalamic-pituitary-thyroid axis (HPT axis) in adult zebrafish. Fish were exposed to a solvent control and three other concentrations of AED (0.2, 2.3, and 23.7 μg/L) for 60 days. Results indicated that AED significantly increased T4 levels but inhibited transcription of some HPT axis-related genes (nis, tpo, tg, dio1, dio2, sult1 st5, pax8, and nkx2.1) in female zebrafish. The adverse effects of AED on the thyroid system in males were very low, only affecting down-regulation of the tshb gene and up-regulation of the thrb gene. The overall results demonstrated that AED interferes with the thyroid endocrine system in fish.
- Published
- 2021
- Full Text
- View/download PDF
117. Circulating endogenous sex steroids and risk of differentiated thyroid carcinoma in men and women.
- Author
-
Rinaldi S, Dossus L, Keski-Rahkonen P, Kiss A, Navionis AS, Biessy C, Travis R, Weiderpass E, Romieu I, Eriksen AK, Tjonneland A, Kvaskoff M, Canonico M, Truong T, Katzke V, Kaaks R, Catalano A, Panico S, Masala G, Tumino R, Lukic M, Olsen KS, Zamora-Ros R, Santiuste C, Aizpurua Atxega A, Guevara M, Rodriguez-Barranco M, Sandstrom M, Hennings J, Almquist M, Aglago Kouassivi E, Christakoudi S, Gunter M, and Franceschi S
- Subjects
- Male, Female, Humans, Androstenedione, Progesterone, Prospective Studies, Gonadal Steroid Hormones, Estradiol, Estrone, Testosterone, Sex Hormone-Binding Globulin metabolism, Thyroid Neoplasms epidemiology, Adenocarcinoma
- Abstract
Thyroid cancer (TC) is substantially more common in women than in men, pointing to a possible role of sex steroid hormones. We investigated the association between circulating sex steroid hormones, sex hormone binding globulin (SHBG) and the risk of differentiated TC in men and women within the European Prospective Investigation into Cancer and nutrition (EPIC) cohort. During follow-up, we identified 333 first primary incident cases of differentiated TC (152 in pre/peri-menopausal women, 111 in post-menopausal women, and 70 in men) and 706 cancer-free controls. Women taking exogenous hormones at blood donation were excluded. Plasma concentrations of testosterone, androstenedione, dehydroepiandrosterone, estradiol, estrone and progesterone (in pre-menopausal women only) were performed using liquid chromatography/mass spectrometry method. SHBG concentrations were measured by immunoassay. Odds ratios (ORs) were estimated using conditional logistic regression models adjusted for possible confounders. No significant associations were observed in men and postmenopausal women, while a borderline significant increase in differentiated TC risk was observed with increasing testosterone (adjusted OR T3 vs T1: 1.68, 95% CI: 0.96-2.92, p
trend = .06) and androstenedione concentrations in pre/perimenopausal women (adjusted OR T3 vs T1: 1.78, 95% CI: 0.96-3.30, ptrend = .06, respectively). A borderline decrease in risk was observed for the highest progesterone/estradiol ratio (adjusted OR T3 vs T1: 0.54, 95% CI: 0.28-1.05, ptrend = .07). Overall, our results do not support a major role of circulating sex steroids in the etiology of differentiated TC in post-menopausal women and men but may suggest an involvement of altered sex steroid production in pre-menopausal women., (© 2024 The World Health Organization. The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.)- Published
- 2024
- Full Text
- View/download PDF
118. Gestational age-specific reference intervals for androgens in pregnancy.
- Author
-
Lau SL, Yuen LY, Ho CS, Chan MHM, Ma RCW, and Tam WH
- Abstract
Background: Androgen could impact cervical remodelling during pregnancy, and a higher level is associated with adverse pregnancy outcomes. A population-based gestation age-specific reference interval (RI) of total testosterone (TT), androstenedione (A4), and 17-hydroxyprogesterone (17-OHP) can help to diagnose maternal hyperandrogenism., Methods: We enrolled 600 healthy Chinese women to obtain longitudinal serum samples across gestation. The serum androgen profile was measured by liquid chromatography-tandem mass spectrometry. The equations for medians of TT, A4, and 17-OHP were generated by MedCal, and the variances adjusted for 2-level modeling were generated by MLwiN, a system for the specification and analysis of a range of multilevel models., Results: A4 and TT levels increased across the gestation, and they closely correlated with each other (R = 0.90, P=<0.001), whereas 17-OHP level decreased from 5th gestational week to 16th gestational week and then increased afterward towards the end of pregnancy. Women diagnosed with preeclampsia (PE) were found to have a significantly higher level of A4, TT, and 17-OHP when compared with non-PE cases with p ≤0.01, whereas mothers carrying male versus female fetuses have comparable levels of A4, TT, and 17-OHP., Conclusion: The study highlights a methodology for constructing gestational age-specific TT, A4, and 17-OHP levels to provide a better interpretation of results in a cohort of healthy Chinese women. The observation in PE supports previous findings, and the higher levels of TT, A4, and 17-OHP were observed before the onset of PE., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)
- Published
- 2024
- Full Text
- View/download PDF
119. Liquid vs dried blood matrices: Application to longitudinal monitoring of androstenedione, testosterone, and IGF-1 by LC-MS-based techniques.
- Author
-
Mazzarino M, Al-Mohammed H, Al-Darwish SK, Salama S, Al-Kaabi A, Samsam W, Kraiem S, Botré F, Beotra A, Mohamed-Ali V, and Al-Maadheed M
- Subjects
- Humans, Chromatography, Liquid methods, Liquid Chromatography-Mass Spectrometry, Insulin-Like Growth Factor I, Tandem Mass Spectrometry methods, Testosterone Congeners, Dried Blood Spot Testing methods, Testosterone, Androstenedione
- Abstract
Background: Dried blood spots have recently been approved by the World Anti-Doping Agency as an alternative biological matrix for testing of doping substances. However, their use is limited to the detection of non-threshold compounds without a Minimum Reporting Level due to the numerous issues related to quantitative analyses and the limitation on testing capabilities of a haemolysed matrix., Aim: In this study androstenedione, testosterone and IGF-1 were longitudinally monitored in four different blood matrices to evaluate the potential of liquid capillary blood as an alternative matrix for quantitative determination in doping control analysis., Methodology: The analytical protocols developed to pretreat 20 μL of the blood matrices selected were based: i) for testosterone and androstenedione, on supported liquid extraction for liquid blood matrices, and on ultrasonication in the presence of methanol for dried blood matrices; ii) for IGF-1, proteins precipitation followed by evaporation of the supernatant was used to pretreat both liquid and dried blood matrices. The detection for all the target analytes was performed using liquid chromatography coupled to mass spectrometry. The analytical workflows, once optimized, were fully validated according to the requirements of World Anti-Doping Agency and ISO 17025 standard and used for the analysis of venous (serum) and capillary (liquid plasma and dried whole blood collected using either volumetric or non-volumetric devices) blood samples collected from 7 healthy subjects., Results: The validation results showed satisfactory performance as related to specificity, sensitivity, matrix effects, linearity, accuracy, and precision in all the blood matrices evaluated despite the limited volume of sample used. The analysis of the different blood matrices collected from the subjects showed non-significant differences between the levels of testosterone and androstenedione measured in dried (fixed volume collected) and liquid matrices. An acceptable underestimation (lower than 15 %) was observed in capillary plasma compared to venous serum. The testosterone/androstenedione ratio was similar in all the blood matrices considered (bias lower than 5 %), indicating this parameter was not affected by either the blood matrix or collection device selected. For IGF-1, the levels measured in liquid blood matrices differed significantly (bias higher than 20 %) from those measured in dried whole blood matrices, suggesting haemolyzed blood might represent a challenge for the determination of macromolecules, mainly due to the complexity of the whole blood matrix in comparison to plasma/serum., Novelty: The outcomes of our study suggest that liquid capillary blood might open new avenues to blood microsampling in doping control field. It represents an efficient alternative to overcome the issues related to venous blood and dried blood spot sampling. Furthermore, it also allows greater frequency of blood sampling, with minor discomfort and without needing a phlebotomist, for analyses that can only be performed in blood samples, with an increased probability to detect and report Adverse Analytical Finding., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
120. The effect of androstenedione supplementation on testosterone, estradiol, body composition, and lipid profile: a systematic review and meta-analysis of randomized controlled trials
- Author
-
Pang, Qiliang, Jia, Aoyun, Al Masri, Mohammad Khaldoun, Varkaneh, Hamed Kord, Abu-Zaid, Ahmed, and Gao, Xiang
- Published
- 2022
- Full Text
- View/download PDF
121. Requirement for oxytocin augmentation in spontaneous parturition is associated with the maternal serum steroid hormones assessed by liquid chromatography coupled to the tandem mass spectrometry.
- Author
-
Kadivnik, Mirta, Debeljak, Željko, Mandić, Dario, Wagner, Jasenka, Kralik, Kristina, Šijanović, Siniša, Muller, Andrijana, and Šerić, Vatroslav
- Subjects
- *
OXYTOCIN , *STATISTICS , *HORMONES , *ADRENOCORTICAL hormones , *LIQUID chromatography , *STEROIDS , *MULTIVARIATE analysis , *PREGNANT women , *MANN Whitney U Test , *DEHYDROEPIANDROSTERONE , *MASS spectrometry , *CHI-squared test , *LABOR (Obstetrics) , *LOGISTIC regression analysis , *RECEIVER operating characteristic curves , *ANDROSTENEDIONE , *UTERINE contraction - Abstract
Aim: The aim of research was to evaluate the maternal serum concentration of selected endogenous steroid hormones during spontaneous parturition at term and to determinate their association with the need for oxytocin augmentation. Methods: Blood of 108 healthy pregnant women whose parturition started with the regular spontaneous uterine contractions was drawn at the beginning of the labor. Liquid chromatography coupled to the tandem mass spectrometry device was utilized for measurement of sex hormone binding globulin, aldosterone, androstenedione, cortisol, cortisone, corticosterone, dehydroepiandrosterone, dehydroepiandrosteron sulphate, 17‐hydroxyprogesterone, progesterone, and testosterone. Mann–Whitney U test, chi‐square test, univariate and multivariate logistic regression, and receiver operating characteristic (ROC) analysis were used for the data analysis. Results: Reference ranges of the selected hormones assessed by liquid chromatography coupled to the tandem mass spectrometry in maternal serum were established. Statistically significant differences in the serum concentration of corticosterone, dehydroepiandrosterone, and androstenedione between mothers requiring oxytocin augmentation and the rest of women having spontaneous parturition were found (p = 0.002, p = 0.008, and p = 0.04, respectively). Concentrations were lower in the group of mothers who required oxytocin infusion for progression of labor. ROC analysis showed that all the mothers with dehydroepiandrosterone serum concentration above 21.6 nmol/L have lower chance to use oxytocin infusion for the labor progression (area under the curve (AUC) = 0.649, sensitivity = 71.7%, specificity = 59.6%, p = 0.006). Conclusion: This research provided reference ranges for the selected maternal serum steroid hormones at the beginning of parturition. Association of corticosterone, dehydroepiandrosterone, and androstenedione with the need for the oxytocin infusion usage has been established. Dehydroepiandrosterone could be potential predictor of oxytocin infusion augmentation for progression of the parturition. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
122. 19-hydroxy Steroids in the Aromatase Reaction: Review on Expression and Potential Functions.
- Author
-
Abaffy, Tatjana and Matsunami, Hiroaki
- Subjects
AROMATASE ,ANDROSTENEDIONE ,STEROIDS analysis - Abstract
Scientific evidence related to the aromatase reaction in various biological processes spanning from mid-1960 to today is abundant; however, as our analytical sensitivity increases, a new look at the old chemical reaction is necessary. Here, we review an irreversible aromatase reaction from the substrate androstenedione. It proceeds in 3 consecutive steps. In the first 2 steps, 19-hydroxy steroids are produced. In the third step, estrone is produced. They can dissociate from the enzyme complex and either accumulate in tissues or enter the blood. In this review, we want to highlight the potential importance of these 19-hydroxy steroids in various physiological and pathological conditions. We focus primarily on 19-hydroxy steroids, and in particular on the 19-hydroxyandrostenedione produced by the incomplete aromatase reaction. Using a PubMed database and the search term "aromatase reaction," 19-hydroxylation of androgens and steroid measurements, we detail the chemistry of the aromatase reaction and list previous and current methods used to measure 19-hydroxy steroids. We present evidence of the existence of 19-hydroxy steroids in brain tissue, ovaries, testes, adrenal glands, prostate cancer, as well as during pregnancy and parturition and in Cushing's disease. Based on the available literature, a potential involvement of 19-hydroxy steroids in the brain differentiation process, sperm motility, ovarian function, and hypertension is suggested and warrants future research. We hope that with the advancement of highly specific and sensitive analytical methods, future research into 19-hydroxy steroids will be encouraged, as much remains to be learned and discovered. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
123. Two aromatase inhibitors inhibit the ability of a third to promote mating in male rats
- Author
-
Yahr, Pauline
- Subjects
Biological Psychology ,Biological Sciences ,Psychology ,Cancer ,Estrogen ,Androgens ,Androstatrienes ,Androstenedione ,Animals ,Aromatase Inhibitors ,Drug Interactions ,Estradiol ,Estrone ,Fadrozole ,Female ,Male ,Rats ,Rats ,Long-Evans ,Rats ,Sprague-Dawley ,Reproduction ,Sexual Behavior ,Animal ,Testosterone ,1 ,4 ,6-Androstatriene-3 ,17-dione ,6α-Fluorotestosterone ,6α-Halogenated androgen ,Aromatase ,Male sex behavior ,Medical and Health Sciences ,Behavioral Science & Comparative Psychology ,Biological sciences ,Biomedical and clinical sciences - Abstract
Aromatase, the enzyme that aromatizes androstenedione (A) to estrone and testosterone (T) to estradiol (E), affects androgen control of male sex behavior in many vertebrates. In male monkeys, rats and quail, E mimics the ability of T to promote mating, and aromatase inhibitors block mating induced by T but not E. Aromatase inhibitors include androgens with different A-rings than T and A, e.g., 1,4,6-androstatriene-3,17-dione (ATD), azoles, e.g., fadrozole, and androgens α-halogenated at carbon 6, e.g., 6α-bromoA, 6α-fluoroA and 6α-fluoroT. 6α-FluoroT is the only 6α-halogenated androgen studied in regard to mating. It promotes mating in male rats and quail and was studied, before it was known to inhibit aromatase, because it cannot be aromatized yet has the same A-ring as T. 6α-FluoroT might promote mating by binding estrogen receptors (ER) directly, i.e., unassisted, or by metabolism to an androgen that binds ER. Since neither process would require aromatase, this study tested both hypotheses by determining how mating induced in castrated male rats by 6α-fluoroT is affected by ATD and fadrozole. Both aromatase inhibitors inhibited the effects of 6α-fluoroT on mating. Thus, 6α-fluoroT does not promote mating by direct ER binding or metabolism to another androgen. Since aromatase underlies a process in which 6α-fluoroT, unlike most nonaromatizable androgens, mimics T effects on male sex behavior, the process must involve a feature that 6α-fluoroT shares with T but not other nonaromatizable androgens. A-ring structure is a candidate. A hypothesis is also offered for how aromatase may participate without aromatizing the androgen.
- Published
- 2015
124. Effect of Finasteride on Serum Androstenedione and Risk of Prostate Cancer Within the Prostate Cancer Prevention Trial: Differential Effect on High- and Low-grade Disease
- Author
-
Hoque, Ashraful, Yao, Song, Till, Cathee, Kristal, Alan R, Goodman, Phyllis J, Hsing, Ann W, Tangen, Catherine M, Platz, Elizabeth A, Stanczyk, Frank Z, Reichardt, Juergen KV, vanBokhoven, Adrie, Neuhouser, Marian L, Santella, Regina M, Figg, William D, Price, Douglas K, Parnes, Howard L, Lippman, Scott M, Ambrosone, Christine B, and Thompson, Ian M
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Prostate Cancer ,Urologic Diseases ,Aging ,Cancer ,Prevention ,Clinical Trials and Supportive Activities ,Clinical Research ,Androstenedione ,Case-Control Studies ,Double-Blind Method ,Finasteride ,Humans ,Male ,Middle Aged ,Neoplasm Grading ,Prostatic Neoplasms ,Risk Assessment ,Urology & Nephrology ,Clinical sciences - Abstract
ObjectiveTo evaluate the effect of finasteride on serum androst-4-ene-3,17-dione (androstenedione) and its association with prostate cancer risk among subjects who participated in the Prostate Cancer Prevention Trial.MethodsWe analyzed serum androstenedione levels in 317 prostate cancer cases and 353 controls, nested in the Prostate Cancer Prevention Trial, a randomized placebo-controlled trial that found finasteride decreased prostate cancer risk. Androstenedione is the second most important circulating androgen in men besides testosterone and also a substrate for 5α-reductase enzyme.ResultsWe observed a 22% increase in androstenedione levels compared with the baseline values in subjects who were treated with finasteride for 3 years. This significant increase did not vary by case-control status. Adjusted odds ratio and 95% confidence interval for the third tertile of absolute change in androstenedione levels compared with the first tertile were 0.42 (95% confidence interval, 0.19-0.94) for low-grade (Gleason score
- Published
- 2015
125. AR collaborates with ERα in aromatase inhibitor-resistant breast cancer
- Author
-
Rechoum, Yassine, Rovito, Daniela, Iacopetta, Domenico, Barone, Ines, Andò, Sebastiano, Weigel, Nancy L, O’Malley, Bert W, Brown, Powel H, and Fuqua, Suzanne AW
- Subjects
Cancer ,Estrogen ,Breast Cancer ,Development of treatments and therapeutic interventions ,5.1 Pharmaceuticals ,Anastrozole ,Androstenedione ,Aromatase Inhibitors ,Breast Neoplasms ,Drug Resistance ,Neoplasm ,Estradiol ,Estrogen Receptor Antagonists ,Estrogen Receptor alpha ,Female ,Fulvestrant ,Humans ,MCF-7 Cells ,Nitriles ,Phosphorylation ,Proto-Oncogene Proteins c-akt ,Receptor ,IGF Type 1 ,Receptors ,Androgen ,Tamoxifen ,Triazoles ,Clinical Sciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
Androgen receptor (AR) is an attractive target in breast cancer because of its frequent expression in all the molecular subtypes, especially in estrogen receptor (ER)-positive luminal breast cancers. We have previously shown a role for AR overexpression in tamoxifen resistance. We engineered ER-positive MCF-7 cells to overexpress aromatase and AR (MCF-7 AR Arom cells) to explore the role of AR in aromatase inhibitor (AI) resistance. Androstendione (AD) was used as a substrate for aromatization to estrogen. The nonsteroidal AI anastrazole (Ana) inhibited AD-stimulated growth and ER transcriptional activity in MCF-7 Arom cells, but not in MCF-7 AR Arom cells. Enhanced activation of pIGF-1R and pAKT was found in AR-overexpressing cells, and their inhibitors restored sensitivity to Ana, suggesting that these pathways represent escape survival mechanisms. Sensitivity to Ana was restored with AR antagonists, or the antiestrogen fulvestrant. These results suggest that both AR and ERα must be blocked to restore sensitivity to hormonal therapies in AR-overexpressing ERα-positive breast cancers. AR contributed to ERα transcriptional activity in MCF-7 AR Arom cells, and AR and ERα co-localized in AD + Ana-treated cells, suggesting cooperation between the two receptors. AR-mediated resistance was associated with a failure to block ER transcriptional activity and enhanced up-regulation of AR and ER-responsive gene expression. Clinically, it may be necessary to block both AR and ERα in patients whose tumors express elevated levels of AR. In addition, inhibitors to the AKT/IGF-1R signaling pathways may provide alternative approaches to block escape pathways and restore hormone sensitivity in resistant breast tumors.
- Published
- 2014
126. An expanded metabolic pathway for androgen production by host-associated bacteria.
- Abstract
A recent preprint abstract suggests that host-associated bacteria may play a role in the production of androgens, which could have implications for androgen-related diseases. The researchers identified a microbial gene in the gut bacterium Clostridium scindens that encodes an enzyme involved in the conversion of androstenedione to epitestosterone. Contrary to current beliefs, the researchers found that epitestosterone is a potent androgen that promotes prostate cancer cell growth. They also discovered that bacterial isolates from urine and prostatectomy tissue are capable of androgen production. These findings highlight the importance of studying microbial biotransformations in relation to androgen-mediated processes and diseases. However, it is important to note that this research has not yet undergone peer review. [Extracted from the article]
- Published
- 2024
127. Studies from Jiangnan University Reveal New Findings on Mycobacteria (Multidirectional Pathway Engineering of Mycobacterium N Eoaurum Ly-2 for the Enhancement of Androstenedione Production From Phytosterols).
- Abstract
A study conducted by researchers at Jiangnan University in Wuxi, China, explores the enhancement of androstenedione production from phytosterols using multidirectional pathway engineering of Mycobacterium neoaurum LY-2. The researchers found that by knocking out the nonessential gene KasB and exploring key enzymes involved in androstenedione synthesis, they were able to increase production by 21.0%. Additionally, the heterologous expression of Vitreoscilla hemoglobin (VHb) in Mycobacterium neoaurum LY-2 further increased androstenedione concentration. The recombinant strain LY-2-Delta KasB-hsd4A-pcc-vgb produced an androstenedione concentration of 11.12 g/L when adding 20 g/L phytosterols. This research has been peer-reviewed. [Extracted from the article]
- Published
- 2024
128. Neurocrine Biosciences Announces Publication of Primary CAHtalyst(TM) Pediatric Phase 3 Study Results of Crinecerfont for the Treatment of CAH in The New England Journal of Medicine.
- Subjects
ADRENOCORTICAL hormones ,LIFE sciences ,WEIGHT loss ,ADRENOGENITAL syndrome ,BIOTECHNOLOGY industries - Abstract
Neurocrine Biosciences has announced that the primary study results from its CAHtalyst Pediatric Phase 3 study on crinecerfont for the treatment of congenital adrenal hyperplasia (CAH) have been published in The New England Journal of Medicine. The study met the primary and key secondary endpoints related to androgen reduction and glucocorticoid dose reduction while maintaining androgen control. The results suggest that crinecerfont could be a potential non-glucocorticoid therapeutic approach for children with CAH, as it showed favorable trends in reducing the consequences of long-term supraphysiologic glucocorticoid therapy and androgen excess. [Extracted from the article]
- Published
- 2024
129. Findings from Mahidol University in Corpus Luteum Hormones Reported (The Influence of IGF-1, Progesterone, Androstenedione, Aromatase, and Estrogen in Successful and Unsuccessful IVF Treatments).
- Abstract
A study conducted by researchers at Mahidol University in Bangkok, Thailand, explored the influence of various hormones on the success of in vitro fertilization (IVF) treatments. The study compared levels of insulin-like growth factor 1 (IGF-1), progesterone (P4), androstenedione, aromatase, and estrogen (E2) in follicular fluid (FF) between subjects with successful and unsuccessful outcomes. The researchers found that unsuccessful pregnancies had lower levels of androstenedione but higher levels of aromatase and IGF-1 in both FF and serum, suggesting a decreased substrate availability for estrogen production in subjects with poor ovarian response. The study also found that IGF-1, P4, androstenedione, and E2 were likely synthesized primarily in FF rather than serum. This research provides insights into the hormonal factors that may impact the success of IVF treatments. [Extracted from the article]
- Published
- 2024
130. Data from Slovak University of Agriculture Advance Knowledge in Cholesterol (The effect of Naringenin on the Testicular Tissue Activity in Mice).
- Abstract
A recent report from the Slovak University of Agriculture discusses the potential therapeutic effects of naringenin, a flavonoid found in grapefruits and other fruits and vegetables. The study aimed to explore the effects of naringenin on testicular tissue activity in mice, specifically its impact on the production of testosterone, androstenedione, dehydroepiandrosterone, and cholesterol. The researchers found that naringenin had a slight increase in testosterone production, with the highest increase observed at a concentration of 10 mol/L. Additionally, naringenin had a significant effect on androstenedione production and increased cholesterol levels. The study suggests that naringenin may have beneficial effects on steroid hormone production and could potentially be used in the management of male reproductive dysfunction. [Extracted from the article]
- Published
- 2024
131. University of Bari A. Moro Reports Findings in Congenital Adrenal Hyperplasia (Increased risk of nephrolithiasis: an emerging issue in children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency).
- Subjects
ADRENOGENITAL syndrome ,KIDNEY stones ,GENITOURINARY diseases ,URINARY organ diseases ,CONGENITAL disorders - Abstract
A report from the University of Bari A. Moro in Italy discusses the increased risk of nephrolithiasis (kidney stones) in children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The study involved 52 children with CAH and found that the incidence of nephrolithiasis was 17.3% at the beginning of the study and decreased over time. The researchers suggest that regular screening of kidney ultrasounds may be indicated for these patients. Further research is needed to understand the causes and risk factors for this condition. [Extracted from the article]
- Published
- 2024
132. Patent Application Titled "Compositions And Methods For Treatment Of Hidradenitis Suppurativa" Published Online (USPTO 20240091209).
- Abstract
The US Patent and Trademark Office has published a patent application titled "Compositions And Methods For Treatment Of Hidradenitis Suppurativa." The application, filed by inventors Ofer A. GOREN and John MCCOY and assigned to Suzhou Kintor Pharmaceuticals Inc., discusses the use of anti-androgen medications, specifically proxalutamide, for the treatment and prevention of hidradenitis suppurativa. The method involves administering an anti-androgen composition to the subject, which may include other medications or vaccines. Hidradenitis suppurativa is a chronic skin disease characterized by painful nodules and abscesses, and this patent application addresses the need for a new treatment option. The application provides detailed information about the method, composition, and related claims, as well as a kit for treating or preventing the condition. [Extracted from the article]
- Published
- 2024
133. Inverse association of certain seminal phthalate metabolites with semen quality may be mediated by androgen synthesis: A cross-sectional study from the South China
- Author
-
Guanxiang Yuan, Yuxing Zeng, Gang Hu, Yu Liu, Lan Wei, Peiyi Liu, Guihua Liu, and Jinquan Cheng
- Subjects
Phthalate metabolite ,Androgen synthesis ,Androstenedione ,Mono butyl phthalate ,Sperm motility ,Environmental sciences ,GE1-350 - Abstract
Background: Several in vitro and in vivo studies have demonstrated the effects of phthalates on androgen synthesis, and the adverse outcomes of phthalate exposure on male reproductive function have been reported. However, the direct relationship among these three factors remains unknown. Objective: To explore the potential roles of steroids involved in androgen synthesis in the association between phthalate exposure and semen quality. Methods: Eighteen phthalate metabolites (mPAEs) and nine steroids were analyzed in semen samples of 403 male participants aged 18–54 years from a hospital in Shenzhen, China. The associations across phthalate metabolites, steroids, and eleven semen quality parameters were evaluated by multivariate linear regression and logistical regression models. The potential contributions of steroids to the associations between phthalate metabolites and semen quality outcomes were explored by mediation effect analysis. Results: In this cross-sectional study, mono-n-butyl phthalate (MnBP) was inversely associated with nine continuous semen quality parameters in a dose-dependent manner (all p for trend
- Published
- 2021
- Full Text
- View/download PDF
134. Consumption of bitter apricot seeds affects lipid and endocrine profile in women.
- Author
-
Kopčeková, Jana, Kováčiková, Eva, Kováčik, Anton, Kolesárová, Anna, Mrázová, Jana, Chlebo, Peter, and Kolesárová, Adriana
- Subjects
- *
FOOD additives , *INHIBIN , *APRICOT , *ARTIFICIAL foods , *BIOACTIVE compounds , *BLOOD lipids - Abstract
Natural products have been attracting increasing attention in human diet, both due to the possible negative effects of synthetic food additives on human health and the increased consumer perception. Apricot seeds contain a wide variety of bioactive components and their consumption is associated with a reduced risk of chronic diseases. The objective of the present study was to evaluate the effect of consumption of bitter apricot seeds on blood lipid and endocrine profile in Slovak women (n = 18, 41.60 ± 11.28 years) of reproductive age. Volunteers consumed 60 mg.kg−1 of body weight of bitter apricot seeds divided into 8-12 doses daily for 42 days. During the experiment, three blood collections were carried out (at the beginning of the experiment - day 0, and after 21 and 42 days of consumption apricot seeds). Lipid profile was measured in terms of – total cholesterol (T-C, enzymatic photometric method), low-density cholesterol (LDL-C, calculated using the Friedewald equation), high-density cholesterol (HDL-C, direct clearance method), triglycerides (TG, enzymatic colorimetric method) whereas endocrine profile - follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), progesterone (P4), 17β-estradiol (E2), testosterone, and androstenedione was assessed by ELISA. The blood levels of T-C, HDL-C and T-C did not change significantly (P > 0.05), however, the level of LDL-C decreased significantly (P < 0.05) after 42 days. On the other hand, there was a significant (P < 0.05) increase of T-C and TG after 21 days. The blood level of FSH, testosterone and androstenedione increased significantly (P < 0.05) although the levels of LH, PRL, P4 and E2 did not change (P > 0.05) after 42 days. The level of PRL and testosterone significantly (P < 0.05) increased and E2 significantly decreased after 21 days of apricot seeds consumption. The study suggests that daily consumption of apricot seeds may affect plasma lipid and endocrine profile in women of reproductive age. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
135. Histological and transcriptional effects of androstenedione in adult zebrafish (Danio rerio).
- Author
-
Liang, Yan‐Qiu, Pan, Chang‐Gui, Xie, Linchun, Huo, Jialiang, Yang, Jiahao, Lan, Tianhong, Dong, Zhongdian, and Duan, Meina
- Subjects
ZEBRA danio ,BRACHYDANIO ,ANDROSTENEDIONE ,GENES ,SEX differentiation (Embryology) ,GONADS - Abstract
As a natural androgen, androstenedione (AED) may pose potential risks to aquatic organisms due to its ubiquitousness in aquatic environments. Here we assessed the adverse effects of AED on histology of gonads, as well as mRNA expression levels of 34 genes concerned with hypothalamic‐pituitary‐gonadal (HPG) axis, germ‐cell differentiation and sex differentiation in zebrafish (Danio rerio). Adult zebrafish were exposed to solvent control and three measured concentrations of 0.2, 2.3 and 23.7 μg/L AED for 60 days. The results showed that AED did not induce any obvious histological effects in the ovaries and testes. Of the investigated genes, transcriptional expression levels of amh and cyp11c1 genes in the ovaries of females were significantly increased by AED at 2.3 or 23.7 μg/L. However, different exposure concentrations of AED significantly inhibited mRNA expression of gnrh3, atf4b1 and cyp19a1b in the brain of males. In the testes of males, AED at 2.3 μg/L led to a significant induction of sox9b gene, but it at 23.7 μg/L down‐regulated nr5a1b gene. These observed transcriptional changes indicated that AED could pose potential androgenic effects in zebrafish. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
136. The glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 catalyzes the activation of testosterone.
- Author
-
Oestlund, Imken, Snoep, Jacky, Schiffer, Lina, Wabitsch, Martin, Arlt, Wiebke, and Storbeck, Karl-Heinz
- Subjects
- *
TESTOSTERONE , *ENZYMES , *MOLECULAR docking , *BIOSYNTHESIS , *ANDROSTENEDIONE , *GONADS - Abstract
Testosterone biosynthesis from its precursor androstenedione is thought to be exclusively catalysed by the 17β-hydroxysteroid dehydrogenases—HSD17B3 in testes, and AKR1C3 in the ovary, adrenal and peripheral tissues. Here we show for the first time that the glucocorticoid activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1) can also catalyse the 17β-reduction of androstenedione to testosterone, using a combination of in vitro enzyme kinetic assays, mathematical modelling, and molecular docking analysis. Furthermore, we show that co-expression of HSD11B1 and AKR1C3 increases testosterone production several-fold compared to the rate observed with AKR1C3 only, and that HSD11B1 is likely to contribute significantly to testosterone production in peripheral tissues. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
137. Exploring the molecular mechanism of Chlorella vulgaris in response to androstenedione exposure based on genes continuously up-regulated in transcription analysis.
- Author
-
Yu, Haiyang, Chen, Xue, Du, Xinxin, Chang, Yanhong, Sun, Shuang, Tang, Shaoyu, Du, Qiuli, and Song, Wenlu
- Subjects
CHLORELLA vulgaris ,HORMONE synthesis ,ANDROSTENEDIONE ,PHENOTYPIC plasticity ,CONCENTRATION gradient - Abstract
Androstenedione (ADSD) is one of the widely detected androgens in diverse aquatic environments. However, there were few reports on the molecular mechanism of Chlorella vulgaris exposure to ADSD. In our previous research, we have investigated the genes associated with chlorophyll metabolism in Chlorella vulgaris response to ADSD. In this study, we focus on continuously up-regulated genes to explore the mechanism underlying Chlorella vulgaris resistance to ADSD toxicity. Chlorella vulgaris was exposed to ADSD with five concentration gradients. The continuously up-regulated genes were enriched by Series Test of Cluster (STC) analysis and verified by qRT-PCR. Microalgae Super Oxidase Dimutase (SOD) and Microalgae Malonic dialdehyde (MDA), two indicators of oxidative stress, were determined by ELISA after exposure to ADSD. The results showed that ADSD can stimulate the production of extracellular polymeric substances (EPS) and lead to enlargement in the cell body of Chlorella vulgaris. In addition, steroid biosynthesis and oxidoreductase activity processes were consistently up-regulated upon exposure to ADSD. In conclusion, our study highlighted the crucial role of phenotypic modification, hormone synthesis, and redox mechanisms in protecting Chlorella vulgaris cells from the harmful effects of ADSD contamination. [Display omitted] • ADSD exposure can cause EPS increase and cell body enlargement. • Alterations phenotypic traits are crucial for chlorella withstand ADSD toxic. • Steroid biosynthesis was up-regulated after ADSD exposure. • Oxidoreductase activity was up-regulated after ADSD exposure. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
138. Influence of ethanol consumption and food intake on serum concentrations of endogenous steroids.
- Author
-
Thieme, Detlef, Krumbholz, Aniko, Bidlingmaier, Martin, Geffert, Christoph, Hameder, Annika, Stöver, Andreas, Graw, Matthias, and Keiler, Annekathrin M.
- Subjects
- *
FOOD consumption , *STEROIDS , *ALCOHOL drinking , *ETHANOL , *BLOOD sampling , *BODYBUILDERS - Abstract
• Influence of ethanol consumption and food intake on serum concentrations of endogenous steroids. • Ethanol consumption increased testosterone/androstenedione ratio in blood. • Meal-induced ACTH and cortisol peaks coincided with pulsatile androstenedione peaks. • Female testosterone levels are more susceptible to perturbations by ethanol or ACTH. Steroid biosynthesis and biotransformation are based on a cascade of enzymatic processes being highly sensitive to various external influences. Amongst those, ethanol was shown to affect testosterone metabolism. For doping analyses, athlete steroid profiles comprise seven urinary steroid metabolites, of which relevant ratios are significantly increased following ethanol consumption. This effect is presumably based on the lack of hepatic NAD+-coenzyme as a consequence of ethanol oxidation. Only recently, testosterone (T) and androstenedione (A4) blood profiles have been introduced as additional approach for doping control. However, a potential influence of ethanol intake on testosterone biosynthesis and thus on blood steroid profiles has not been investigated so far. Therefore, steroid concentrations from 10 males and 10 females receiving an ethanol infusion up to a breath alcohol concentration of 0.5 mg/L which was hold as a plateau for two hours were conducted. Blood samples were drawn every 15 min for steroid quantification. An ethanol-dependent T/A4 increase up to 385 % resulting from A4 suppression was observed in 14 volunteers. In addition, we observed sporadic A4 increases coinciding with cortisol and ACTH pulses pointing to a meal-induced adrenal stimulation. While testosterone levels in males showed diurnal variation solely, testosterone levels in some females were found to be susceptible to ethanol- and ACTH-dependent perturbations, which is thought to be due to its predominant adrenal synthesis in females. In conclusion, the results of the present study emphasize the importance of blood sampling at a sufficient time interval from food and ethanol intake. This is of interest if T and A4 are used for diagnostics in doping control. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
139. Resveratrol potentiates effects of simvastatin on inhibition of rat ovarian theca-interstitial cells steroidogenesis.
- Author
-
Ortega, Israel, Villanueva, Jesus A, Wong, Donna H, Cress, Amanda B, Sokalska, Anna, Stanley, Scott D, and Duleba, Antoni J
- Subjects
Theca Cells ,Cells ,Cultured ,Animals ,Rats ,Sprague-Dawley ,Stilbenes ,Simvastatin ,Androsterone ,Androstenedione ,Steroid 17-alpha-Hydroxylase ,RNA ,Messenger ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Down-Regulation ,Gene Expression Regulation ,Enzymologic ,Dose-Response Relationship ,Drug ,Drug Synergism ,Time Factors ,Female ,Resveratrol ,Androgens ,CYP17A1 ,Ovarian theca-interstitial cells ,Steroidogenesis ,Cells ,Cultured ,Rats ,Sprague-Dawley ,RNA ,Messenger ,Gene Expression Regulation ,Enzymologic ,Dose-Response Relationship ,Drug - Abstract
BackgroundPolycystic ovary syndrome (PCOS) is characterized by ovarian enlargement, hyperplastic theca compartment and increased androgen production due to, at least in part, excessive expression of several key genes involved in steroidogenesis. Previously, our group has demonstrated that simvastatin, competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), a rate-limiting step of the mevalonate pathway, reduces rat-theca interstitial cell steroidogenesis by inhibiting Cyp17a1 gene expression, the key enzyme of the androgen biosynthesis pathway. Recently, we demonstrated that resveratrol, a bioflavonoid abundant in red grapes, decreases rat theca-interstitial cell steroidogenesis and this suppressive effect is mediated through mechanisms independent of the mevalonate pathway. The present study evaluated the effect of combining simvastatin and resveratrol treatments on rat theca-interstitial cell steroidogenesis.MethodsRat theca-interstitial cells isolated from 30 day-old female rats were cultured for up to 48 h with or without simvastatin (1 μM) and/or resveratrol (3-10 μM). Steroidogenic enzymes gene expression was evaluated by quantitative real time PCR and steroid levels were measured by liquid chromatography-mass spectrometry. Comparisons between groups were performed using ANOVA and Tukey test.ResultsResveratrol potentiated inhibitory effects of simvastatin on androstenedione and androsterone production in theca-interstitial cells. This suppressive effect correlated with profound inhibition in Cyp17a1 mRNA expression in the presence of a combination of resveratrol and simvastatin.ConclusionsThe present findings indicate that resveratrol potentiates the simvastatin-induced inhibitory effect on theca-interstitial cell androgen production, raising the possibility of development of novel treatments of PCOS.
- Published
- 2014
140. Biotransformation of Phytosterols into Androstenedione—A Technological Prospecting Study
- Author
-
Victor Oliveira Nunes, Nathália de Castro Vanzellotti, Jully Lacerda Fraga, Fernando Luiz Pellegrini Pessoa, Tatiana Felix Ferreira, and Priscilla Filomena Fonseca Amaral
- Subjects
steroid ,androstenedione ,biosynthesis ,Mycobacterium ,phytosterol ,pharmaceutical ,Organic chemistry ,QD241-441 - Abstract
Androstenedione (AD) is a key intermediate in the body’s steroid metabolism, used as a precursor for several steroid substances, such as testosterone, estradiol, ethinyl estradiol, testolactone, progesterone, cortisone, cortisol, prednisone, and prednisolone. The world market for AD and ADD (androstadienedione) exceeds 1000 tons per year, which stimulates the pharmaceutical industry’s search for newer and cheaper raw materials to produce steroidal compounds. In light of this interest, we aimed to investigate the progress of AD biosynthesis from phytosterols by prospecting scientific articles (Scopus, Web of Science, and Google Scholar databases) and patents (USPTO database). A wide variety of articles and patents involving AD and phytosterol were found in the last few decades, resulting in 108 relevant articles (from January 2000 to December 2021) and 23 patents of interest (from January 1976 to December 2021). The separation of these documents into macro, meso, and micro categories revealed that most studies (articles) are performed in China (54.8%) and in universities (76%), while patents are mostly granted to United States companies. It also highlights the fact that AD production studies are focused on “process improvement” techniques and on possible modifications of the “microorganism” involved in biosynthesis (64 and 62 documents, respectively). The most-reported “process improvement” technique is “chemical addition” (40%), which means that the addition of solvents, surfactants, cofactors, inducers, ionic liquids, etc., can significantly increase AD production. Microbial genetic modifications stand out in the “microorganism” category because this strategy improves AD yield considerably. These documents also revealed the main aspects of AD and ADD biosynthesis: Mycolicibacterium sp. (basonym: Mycobacterium sp.) (40%) and Mycolicibacterium neoaurum (known previously as Mycobacterium neoaurum) (32%) are the most recurrent species studied. Microbial incubation temperatures can vary from 29 °C to 37 °C; incubation can last from 72 h to 14 days; the mixture is agitated at 140 to 220 rpm; vegetable oils, mainly soybean, can be used as the source of a mixture of phytosterols. In general, the results obtained in the present technological prospecting study are fundamental to mapping the possibilities of AD biosynthesis process optimization, as well as to identifying emerging technologies and methodologies in this scenario.
- Published
- 2022
- Full Text
- View/download PDF
141. Endocrinology of the Fetal Testis
- Author
-
Ivell, Richard, Anand-Ivell, Ravinder, Morley, Steven D., Lenzi, Andrea, Series editor, Jannini, Emmanuele A., Series editor, Simoni, Manuela, editor, and Huhtaniemi, Ilpo T., editor
- Published
- 2017
- Full Text
- View/download PDF
142. Follicular Fluid Hormone Profiles in Natural Cycle IVF Patients During Follicular Phase
- Author
-
Ellissa Baskind, N., Sharma, Vinay, Chian, Ri-Cheng, editor, Nargund, Geeta, editor, and Huang, Jack Y. J., editor
- Published
- 2017
- Full Text
- View/download PDF
143. An integrated PK‐PD model for cortisol and the 17‐hydroxyprogesterone and androstenedione biomarkers in children with congenital adrenal hyperplasia.
- Author
-
Al‐Kofahi, Mahmoud, Ahmed, Mariam A., Jaber, Mutaz M., Tran, Thang N., Willis, Brian A., Zimmerman, Cheryl L., Gonzalez‐Bolanos, Maria T., Brundage, Richard C., and Sarafoglou, Kyriakie
- Subjects
- *
ADRENOGENITAL syndrome , *HYDROCORTISONE , *ANDROSTENEDIONE , *MEDICAL personnel , *BIOMARKERS , *CIRCADIAN rhythms - Abstract
Aims: The aim of this study was to characterize the pharmacokinetic/pharmacodynamic relationships of cortisol and the adrenal biomarkers 17‐hydroxyprogesterone and androstenedione in children with congenital adrenal hyperplasia (CAH). Methods: A nonlinear mixed‐effect modelling approach was used to analyse cortisol, 17‐hydroxyprogesterone and androstenedione concentrations obtained over 6 hours from children with CAH (n = 50). A circadian rhythm was evident and the model leveraged literature information on circadian rhythm in untreated children with CAH. Indirect response models were applied in which cortisol inhibited the production rate of all three compounds using an Imax model. Results: Cortisol was characterized by a one‐compartment model with apparent clearance and volume of distribution estimated at 22.9 L/h/70 kg and 41.1 L/70 kg, respectively. The IC50 values of cortisol concentrations for cortisol, 17‐hydroxyprogesterone and androstenedione were estimated to be 1.36, 0.45 and 0.75 μg/dL, respectively. The inhibitory effect was found to be more potent on 17OHP than D4A, and the IC50 values were higher in salt‐wasting subjects than simple virilizers. Production rates of cortisol, 17‐hydroxyprogesterone and androstenedione were higher in simple‐virilizer subjects. Half‐lives of cortisol, 17‐hydroxyprogesterone and androstenedione were 60, 47 and 77 minutes, respectively. Conclusion: Rapidly changing biomarker responses to cortisol concentrations highlight that single measurements provide volatile information about a child's disease control. Our model closely captured observed cortisol, 17‐hydroxyprogesterone and androstenedione concentrations. It can be used to predict concentrations over 24 hours and allows many novel exposure metrics to be calculated, e.g., AUC, AUC‐above‐threshold, time‐within‐range, etc. Our long‐range goal is to uncover dose–exposure–outcome relationships that clinicians can use in adjusting hydrocortisone dose and timing. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
144. Block and Replace--A New Therapeutic Concept in Congenital Adrenal Hyperplasia?
- Author
-
Reisch, Nicole
- Subjects
ADRENOGENITAL syndrome ,BONE health ,ADRENAL glands ,SPERMATOGENESIS - Abstract
The article discusses the current treatment challenges and potential new therapeutic concepts for patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The traditional treatment involves hydrocortisone given thrice daily, which can lead to various morbidities and suboptimal outcomes. Two emerging concepts are being explored: a modified-release hydrocortisone preparation that mimics the normal cortisol rhythm and a corticotropin-releasing factor type 1 (CRF1) receptor antagonist that aims to reduce the need for supraphysiological glucocorticoid doses. These new approaches have shown promising results in reducing hormonal imbalances and may lead to more individualized and physiologic treatment for improved long-term outcomes in CAH patients. [Extracted from the article]
- Published
- 2022
- Full Text
- View/download PDF
145. Efficient Production of 9,22-Dihydroxy-23,24-bisnorchol-4-ene-3-one from Phytosterols by Modifying Multiple Genes in Mycobacterium fortuitum .
- Author
-
Han S, Liu X, He B, Zhai X, Yuan C, Li Y, Lin W, Wang H, and Zhang B
- Subjects
- Androstenedione, Molar, Progesterone, Mycobacterium fortuitum genetics, Phytosterols
- Abstract
C19 steroids and C22 steroids are vital intermediates for the synthesis of steroid drugs. Compared with C19 steroids, C22 steroids are more suitable for synthesizing progesterone and adrenocortical hormones, albeit less developed. 9,22-dihydroxy-23,24-bisnorchol-4-ene-3-one(9-OHBA), due to its substituents at positions C-9 and C-22, is a beneficial and innovative steroid derivative for synthesizing corticosteroids. We focused on the C22 pathway in Mycobacterium fortuitum ATCC 35855, aiming to develop a productive strain that produces 9-OHBA. We used a mutant strain, MFΔ kstD , that knocked out kstds from Mycobacterium fortuitum ATCC 35855 named MFKD in this study as the original strain. Hsd4A and FadA5 are key enzymes in controlling the C19 metabolic pathway of steroids in Mycobacterium fortuitum ATCC 35855. After knocking out hsd4A , MFKDΔ hsd4A accumulated 81.47% 9-OHBA compared with 4.13% 9-OHBA in the strain MFKD. The double mutant MFKDΔ hsd4A Δ fadA5 further improved the selectivity of 9-OHBA to 95.13%, and 9α-hydroxy-4-androstenedione (9-OHAD) decreased to 0.90% from 4.19%. In the end, we obtained 6.81 g/L 9-OHBA from 10 g/L phytosterols with a molar yield of 80.33%, which showed the best performance compared with formerly reported strains.
- Published
- 2024
- Full Text
- View/download PDF
146. Comparative Study of Insulin Sensitivity and Resistance and Their Correlation with Androgens in Lean and Obese Women with Polycystic Ovary Syndrome.
- Author
-
Misra S, Gada J, Dhole C, Varthakavi P, and Bhagwat N
- Subjects
- Female, Humans, Androgens, Androstenedione, Cross-Sectional Studies, Blood Glucose, Insulin, Obesity complications, Obesity diagnosis, Glucose, Body Mass Index, Insulin Resistance physiology, Polycystic Ovary Syndrome complications
- Abstract
There is a lack of consensus on the optimal screening strategy for insulin resistance (IR), particularly in lean women with polycystic ovary syndrome (PCOS). Therefore, we conducted a cross-sectional study in 80 women with PCOS (28 lean/52 obese) and 80 age- and body mass index (BMI)-matched controls. Using a 5-point 75-g oral glucose tolerance test (OGTT) (0, 30, 60, 90, 120 min), we examined glucose and insulin excursions, IR, insulin sensitivity, beta-cell function (ßF), and the effect of androgens on IR. Lean and obese women with PCOS had similar glucose but higher insulin (except fasting in lean women) and insulin AUC as compared to their respective controls (p < 0.05). Lean women with PCOS were equally insulin-resistant but more hyperinsulinemic than the obese controls (p < 0.05). Although ßF ([1st phase: 481.71 ± 263.53 vs. 430.56 ± 232.37], [2nd phase: 815.16 ± 447.12 vs. 752.66 ± 428.95]) was comparable in lean and obese women with PCOS, lean women had better insulin sensitivity (112.78 ± 66.26 vs. 75.49 ± 55.6) (p < 0.05). Dehydroepiandrosterone sulfate (DHEAS) and androstenedione decreased with increasing BMI in lean women, and this correlated with deteriorating insulin sensitivity and exaggerated hyperinsulinemia. In obese women with PCOS, sex hormone-binding globulin (SHBG) correlated negatively with BMI and hyperinsulinemia, and positively with insulin sensitivity. This data suggests that estimating only fasting insulin may miss IR in lean women with PCOS; hence, additional time points in OGTT will add value to screening for IR. DHEAS and androstenedione may have a beneficial effect on insulin sensitivity and may be used to screen IR in lean women, while SHBG can be used as a predictive marker for IR in obese women with PCOS., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)
- Published
- 2024
- Full Text
- View/download PDF
147. Metabolomics identifies and validates serum androstenedione as novel biomarker for diagnosing primary angle closure glaucoma and predicting the visual field progression.
- Author
-
Li S, Ren J, Jiang Z, Qiu Y, Shao M, Li Y, Wu J, Song Y, Sun X, Gao S, and Cao W
- Subjects
- Humans, Bayes Theorem, Biomarkers, China, Cross-Sectional Studies, Prospective Studies, Visual Fields, Androstenedione, Glaucoma, Angle-Closure diagnosis
- Abstract
Background: Primary angle closure glaucoma (PACG) is the leading cause of irreversible blindness in Asia, and no reliable, effective diagnostic, and predictive biomarkers are used in clinical routines. A growing body of evidence shows metabolic alterations in patients with glaucoma. We aimed to develop and validate potential metabolite biomarkers to diagnose and predict the visual field progression of PACG., Methods: Here, we used a five-phase (discovery phase, validation phase 1, validation phase 2, supplementary phase, and cohort phase) multicenter (EENT hospital, Shanghai Xuhui Central Hospital), cross-sectional, prospective cohort study designed to perform widely targeted metabolomics and chemiluminescence immunoassay to determine candidate biomarkers. Five machine learning (random forest, support vector machine, lasso, K-nearest neighbor, and GaussianNaive Bayes [NB]) approaches were used to identify an optimal algorithm. The discrimination ability was evaluated using the area under the receiver operating characteristic curve (AUC). Calibration was assessed by Hosmer-Lemeshow tests and calibration plots., Results: Studied serum samples were collected from 616 participants, and 1464 metabolites were identified. Machine learning algorithm determines that androstenedione exhibited excellent discrimination and acceptable calibration in discriminating PACG across the discovery phase (discovery set 1, AUCs=1.0 [95% CI, 1.00-1.00]; discovery set 2, AUCs = 0.85 [95% CI, 0.80-0.90]) and validation phases (internal validation, AUCs = 0.86 [95% CI, 0.81-0.91]; external validation, AUCs = 0.87 [95% CI, 0.80-0.95]). Androstenedione also exhibited a higher AUC (0.92-0.98) to discriminate the severity of PACG. In the supplemental phase, serum androstenedione levels were consistent with those in aqueous humor (r=0.82, p=0.038) and significantly (p=0.021) decreased after treatment. Further, cohort phase demonstrates that higher baseline androstenedione levels (hazard ratio = 2.71 [95% CI: 1.199-6.104], p=0.017) were associated with faster visual field progression., Conclusions: Our study identifies serum androstenedione as a potential biomarker for diagnosing PACG and indicating visual field progression., Funding: This work was supported by Youth Medical Talents - Clinical Laboratory Practitioner Program (2022-65), the National Natural Science Foundation of China (82302582), Shanghai Municipal Health Commission Project (20224Y0317), and Higher Education Industry-Academic-Research Innovation Fund of China (2023JQ006)., Competing Interests: SL, JR, ZJ, YQ, MS, YL, JW, YS, XS, SG, WC No competing interests declared, (© 2023, Li, Ren, Jiang et al.)
- Published
- 2024
- Full Text
- View/download PDF
148. Insights From Liquid Chromatography-Mass Spectrometry-Measured Androgens in Indian Women With Polycystic Ovary Syndrome.
- Author
-
Subramaniam K and Kansal N
- Abstract
Introduction: Hyperandrogenemia is the defining feature of polycystic ovary syndrome (PCOS). Increasingly androgens are being advocated to be measured through liquid chromatography-mass spectrometry (LC-MS/MS). The role of LC-MS/MS over immunoassay in diagnosis of PCOS has been debated over a long time. We analyzed the role of androgens as measured by LC-MS/MS in diagnosing women with PCOS., Materials and Methods: We performed a prospective case-control study involving 59 women with PCOS compared with 30 age- and BMI-matched controls., Results: In PCOS phenotypes A-C (hyperandrogenic by definition), 19/47 (40%) had normal testosterone (T) levels but 14/19 (75%) had either elevated androstenedione (A4) or dehydroepiandrosterone. A4 had the highest area under curve (0.89) for diagnosing PCOS followed by T (0.81). Even in the PCOS-D phenotype (sonologic polycystic ovaries + oligomenorrhoea), A4 was significantly higher as compared to controls though still in normal range., Conclusion: A4 had a role in diagnosing hyperandrogenism in women with PCOS. Further studies clarifying the role of androgen profiles in diagnosing PCOS and its cost-effectiveness may be required in the future., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Subramaniam et al.)
- Published
- 2024
- Full Text
- View/download PDF
149. 11-deoxycortisol positively correlates with T cell immune traits in physiological conditions.
- Author
-
Peng C, Jiang X, Jaeger M, van Houten P, van Herwaarden AE, Koeken VACM, Moorlag SJCFM, Mourits VP, Lemmers H, Dijkstra H, Koenen HJPM, Joosten I, van Cranenbroek B, Li Y, Joosten LAB, Netea MG, Netea-Maier RT, and Xu CJ
- Subjects
- Humans, Androstenedione, Steroids, Phenotype, Cortodoxone, Progesterone
- Abstract
Background: Endogenous steroid hormones have significant effects on inflammatory and immune processes, but the immunological activities of steroidogenesis precursors remain largely unexplored., Methods: We conducted a systematic approach to examine the association between steroid hormones profile and immune traits in a cohort of 534 healthy volunteers. Serum concentrations of steroid hormones and their precursors (cortisol, progesterone, testosterone, androstenedione, 11-deoxycortisol and 17-OH progesterone) were determined by liquid chromatography-tandem mass spectrometry. Immune traits were evaluated by quantifying cellular composition of the circulating immune system and ex vivo cytokine responses elicited by major human pathogens and microbial ligands. An independent cohort of 321 individuals was used for validation, followed by in vitro validation experiments., Findings: We observed a positive association between 11-deoxycortisol and lymphoid cellular subsets numbers and function (especially IL-17 response). The association with lymphoid cellularity was validated in an independent validation cohort. In vitro experiments showed that, as compared to androstenedione and 17-OH progesterone, 11-deoxycortisol promoted T cell proliferation and Candida-induced Th17 polarization at physiologically relevant concentrations. Functionally, 11-deoxycortisol-treated T cells displayed a more activated phenotype (PD-L1
high CD25high CD62Llow CD127low ) in response to CD3/CD28 co-stimulation, and downregulated expression of T-bet nuclear transcription factor., Interpretation: Our findings suggest a positive association between 11-deoxycortisol and T-cell function under physiological conditions. Further investigation is needed to explore the potential mechanisms and clinical implications., Funding: Found in acknowledgements., Competing Interests: Declaration of interests The authors declare that there is no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
150. 14 C-radiolabeling of a new steroidal antiandrogen with a C-18 angular methyl extension.
- Author
-
Sancéau JY
- Subjects
- Steroids, Phenols, Phenol, Propylamines, Androstenedione, Androgen Antagonists
- Abstract
The synthesis of a
14 C-labeled C-18 functionalized steroid (as referred as EM-6798) that will serve as a probe for the research of novel antiandrogens has been accomplished. This radioactive steroid was obtained in nine steps by coupling racemic N-cyclohexyl-1-(3'-hydroxy[U-14 C]phenyl)propylamine with protected 18-bromomethyl-3,17-androstenedione. Incorporation of the radiolabel on the C-18 side chain was achieved using commercially available 3-bromo[U-14 C]phenol. Alkylation of N-cyclohexyl-1-(3'-hydroxy[U-14 C]phenyl)propylamine with 3-ethylenedioxy-18-bromomethyl-3,17-androstenedione furnished after reduction and deprotection, [phenyl-U-14 C]EM-6798 in a 20% overall yield from 3-bromo[U-14 C]phenol at a specific activity of 156 μCi/mg with 97.9% radiochemical purity as determined by HPLC., (© 2023 John Wiley & Sons, Ltd.)- Published
- 2024
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.