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No study on the relationship between hepatic steatosis and sex hormone levels in male patients with chronic hepatitis B (CHB) infection has been conducted.We aimed to investigate the association between serum sex hormones and hepatic steatosis among a cohort of males with CHB.In this cross-sectional study, 268 male patients with CHB were enrolled. All participants underwent anthropometric measurement, blood testing, and FibroScan test. Multiple logistic regression analysis was used to investigate the association of serum sex hormones with hepatic steatosis.We included 137 males with and 131 without hepatic steatosis in this study. Subjects with serum testosterone (T) levels in the highest tertile had an odds ratio (OR) (95% confidence interval [CI]) of 0.35 (0.18-0.70) (P for trend=0.003); those with serum prolactin (PRL) levels in the highest tertile had an OR (95%CI) of 0.21 (0.10-0.45) (P for trend0.001); and those with serum estradiol/testosterone (E2/T) in the highest tertile had an OR (95%CI) of 4.02 (1.97-8.20) (P for trend0.001) for hepatic steatosis.Lower serum total T and PRL levels and higher total E2/T are independently associated with presence of hepatic steatosis in male patients with CHB.

Aim: In this study, we aimed to investigate the effects of menopause on serum levels of cortisol, alpha-amylase, dopamine, and prolactin in women with periodontitis and healthy controls.Methods: The study included a total of 80 women. Patients were diagnosed according to the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions criteria. The clinical examination included plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment loss (AL) measurements. The systemic levels of cortisol, alpha-amylase,dopamine, and prolactin were measured biochemically. Data were analyzed statistically. Results: The mean participant age was 44.32±3.23 (range: 33–55) years. The mean PI was 0.98±0.10, GI 0.94±0.31, PD 2.59±0.23 mm, and AL 2.65±0.16 mm. While prolactin levels were statistically significantly lower in menopausal women (p0.05). Levels of cortisol, dopamine and prolactinwere found to be significantly high in women with periodontitis (p

BACKGROUND The impact of estrogen and testosterone on atherosclerotic cardiovascular disease is well known, but the role of the gonadotropins follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) to some extent remain less studied. OBJECTIVES To explore the angiogenic potential of gonadotropins on endothelial colony-forming cells (ECFCs). METHODS We examined the effects of various doses of gonadotropins on ECFCs obtained from cord blood by assessing colony number, proliferation, migration, and sprouting ability. Moreover, we studied thrombin generation in ECFCs exposed to gonadotropins by performing a thrombin generation assay. Finally, we determined the levels of circulating gonadotropins in 30 men, to exclude the effect of estrogen, with lower extremity arterial disease (LEAD), in comparison with age- and sex-matched controls. RESULTS Exposure to FSH, LH, or PRL resulted in an increase in ECFC migration but showed no effect on proliferation or ECFC commitment from cord blood mononuclear cells. Using a three-dimensional fibrin gel assay, we showed that ECFC sprouting was significantly enhanced by gonadotropins. Exposure to FSH also increased the thrombin generation of ECFCs exposed to FSH. Finally, FSH and LH levels in men with LEAD were higher than those in controls. CONCLUSION Gonadotropins increase ECFC-related angiogenesis and may be involved in thrombin generation in cardiovascular disease. Gonadotropins may act as biomarkers; moreover, we hypothesize that gonadotropin-blocking strategies may be a novel interesting therapeutic approach in atherosclerotic cardiovascular disease.

BACKGROUND: IL-18 is known as an interferon-inducing factor that belongs to the IL-1 family, and is synthesized as an inactive precursor protein. OBJECTIVE: The present study aims to investigate the expression of IL-18, IL-18R, R and IL-18 binding protein (BP) mRNA in various types of human pituitary tumors, such as adrenocorticotropic hormone (ACTH), growth hormone (GH), prolactin (PRL), thyroid stimulating hormone (TSH)-producing adenomas and non-function adenomas. METHODS: Pituitary adenoma tissues were obtained during the surgery of 41 patients: nine patients had ACTH-producing pituitary adenomas, nine patients had GH-producing pituitary adenomas, five patients had TSH-producing pituitary adenomas, seven patients had PRL-producing pituitary adenomas, and 11 patients had non-functioning adenomas. The mRNA expression levels of IL-18, IL-18BP, IL-18R and IL-18R were quantified using real-time quantitative PCR. RESULTS: The mRNA expression of IL-18 was significantly higher in ACTH-, GH- and PRL-producing adenomas, when compared to non-function tumors. Similarly, a significantly higher mRNA expression of IL-18BP and IL-18R was observed in ACTH-, GH- and PRL-producing adenomas, when compared with non-functional adenomas. In contrast, no upregulation of IL-18R mRNA was observed in any of the pituitary adenomas. CONCLUSIONS: The mRNA levels of IL-18, IL-18BP and IL-18R are significantly elevated in clinical pituitary tumors, such as ACTH-, GH- and PRL-producing adenomas, when compared to non-functional adenomas. These present results suggest the possibility that IL-18 may be involved in the pathogenesis of pituitary adenoma.

BACKGROUND: Prolactin-releasing peptide(Prl-RP), in addition to stimulating the production of prolactin, interacts with various parts of the central nervous system, participating in the implementation of many functions that are reflected in behavior.AIM: The effect of Prl-RP on the anxiety of white Wistar rats was studied since there were no data in the literature on the relationship between Prl-RP and anxiety.MATERIALS AND METHODS: Anxiety was assessed in two tests. In the elevated plus-maze (EPM), the time spent in the open arms and the number of edge reactions were recorded. In the social preference test, the time spent near a stranger, near a familiar individual, and in neutral territory were recorded.RESULTS: The administration of Prl-RP at a dose of 10-10 M with a volume of 10 µl in each nostril reduced the time spent by the animals in the open arms of the EPM, and the number of edge reactions. For testing the social interaction, animals were pre-selected for high or low levels of anxiety in the EPM. In rats with initially low levels of anxiety, Prl-RP reduced the time spent near a stranger, indicating an increase in anxiety levels. The behavior of rats with initially high levels of anxiety did not change after application of the Prl-RP.CONCLUSION: The results of our experiments indicate that the intranasal administration of Prl-RP increases the anxiety of rats.

Background As the critical tissue of the central nervous system, the brain has been found to be involved in gonad development. Previous studies have suggested that gonadal fate may be affected by the brain. Identifying brain-specific molecular changes that occur during estrodiol-17β (E2) -induced feminization is crucial to our understanding of the molecular control of sex differentiation by the brains of fish. Results In this study, the differential transcriptomic responses of the Takifugu rubripes larvae brain were compared after E2 treatment for 55 days. Our results showed that 514 genes were differentially expressed between E2-treated-XX (E-XX) and Control-XX (C-XX) T. rubripes, while 362 genes were differentially expressed between E2-treated-XY (E-XY) and Control-XY (C-XY). For example, the expression of cyp19a1b, gnrh1 and pgr was significantly up-regulated, while st, sl, tshβ, prl and pit-1, which belong to the growth hormone/prolactin family, were significantly down-regulated after E2 treatment, in both sexes. The arntl1, bhlbe, nr1d2, per1b, per3, cry1, cipc and ciart genes, which are involved in the circadian rhythm, were also found to be altered. Differentially expressed genes (DEGs), which were identified between E-XX and C-XX, were significantly enriched in neuroactive ligand-receptor interaction, arachidonic acid metabolism, cytokine-cytokine receptor interaction and the calcium signaling pathway. The DEGs that were identified between E-XY and C-XY were significantly enriched in tyrosine metabolism, phenylalanine metabolism, arachidonic acid metabolism and linoleic acid metabolism. Conclusion A number of genes and pathways were identified in the brain of E2-treated T. rubripes larvae by RNA-seq. It provided the opportunity for further study on the possible involvement of networks in the brain-pituitary-gonadal axis in sex differentiation in T. rubripes.

Background: Postpartum fatigue is a common disorder worldwide and affects both physical and mental functioning. In breastfeeding women, Prolactin (PRL) is not only involved in immunoregulation, but also responsible for lactation. Prolactin levels in women with chronic fatigue are higher than normal, but a chronic fatigue state inhibits postpartum lactation in humans. Objectives: This paper explored the inhibition mechanism of lactation by postpartum fatigue in rats. Methods: Postpartum fatigue models were built by forcing mother rats to stand in water and divided into 3-hour, 9-hour and 15-hour per day fatigue groups according to the underwater time. Mother rats and their offspring were reunited in a dry cage for 90 minutes every 3 hours for feeding. The expression of PRL, PRL receptor (PRLR), Janus Kinase 2 (JAK 2), and Signal transducers and activators of transcription 5 (STAT5) mRNA were analyzed and the microstructure of mammary gland were observed under light and electron microscopy. Results: The expression of pituitary PRL mRNA and its downstream signaling pathway JAK2 and STAT5 mRNA were down-regulated in the severe postpartum fatigue rats. PRL mRNA responses were dose-related to duration of fatigue. The expression of PRLR mRNA increased. Postpartum fatigue led to functional degeneration of mammary gland. The breast lobules were shrunk and the number of alveoli were decreased. Few milk protein granules and fat droplets were observed in the cytoplasm under transmission electron microscope. Conclusion: Postpartum fatigue inhibits the lactation by down-regulating the expression of PRL and PRL-dependent signaling pathway in rats.

Introduction: Prolactin (PRL) exerts inflammatory and anti-inflammatory properties and is also thought to play an important role in the pathogenesis of neurodegenerative diseases (NDs). However, serum PRL levels in patients with NDs were inconsistent in the research literature. Objective: We aimed to assess the serum PRL levels in patients with NDs. Methods: Electronic databases, including MEDLINE, Embase, Cochrane Library database, clinicaltrials.gov, Web of Science, and Google Scholar, and reference lists of articles were searched up to December 31, 2020. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effect or random-effect model analysis. Results: A total of 36 comparisons out of 29 studies (3 RCTs and 26 case controls) focusing on NDs (including Parkinson’s disease, Alzheimer’s disease, Huntington’s disease [HD], multiple sclerosis [MS], and epilepsy) were reported. The meta-analysis showed that there was no statistically significant difference in serum PRL levels between patients with NDs and healthy controls (SMD = 0.40, 95% CI: −0.16 to 0.96, p = 0.16). Subgroup analysis showed that serum PRL levels in patients with HD and MS were higher than those of healthy controls. Furthermore, patients with NDs aged p = 0.018) than healthy controls. High serum PRL levels were found in subgroups such as the microenzymatic method, Asia, and the Americas. Conclusions: Our meta-analysis showed serum PRL levels in patients with HD and MS were significantly higher than those in healthy controls. Serum PRL levels were associated with age, region, and detection method. Other larger sample studies using more uniform detection methods are necessary to confirm our results.

Prolactin and placental lactogens increase during pregnancy and are involved with many aspects of maternal metabolic adaptation to pregnancy, likely to impact on fetal growth. The aim of this study was to determine whether maternal plasma prolactin or placental lactogen concentrations at 20 weeks of gestation were associated with later birth of small-for-gestational-age babies (SGA). In a nested case–control study, prolactin and placental lactogen in plasma samples obtained at 20 weeks of gestation were compared between 40 women who gave birth to SGA babies and 40 women with uncomplicated pregnancies and size appropriate-for-gestation-age (AGA) babies. Samples were collected as part of the 'screening of pregnancy endpoints' (SCOPE) prospective cohort study. SGA was defined as birthweight s.d., P = 0.036 Student’s t-test) compared to control pregnancies carrying a male fetus. Despite the implications of these lactogenic hormones in maternal metabolism, single measurements of either prolactin or placental lactogen at 20 weeks of gestation are unlikely to be useful biomarkers for SGA pregnancies. Lay summary Early identification during pregnancy of small for gestational age (SGA) babies would enable interventions to lower risk of complications around birth (perinatal), but current detection rates of these at risk babies is low. Pregnancy hormones, prolactin and placental lactogen, are involved in metabolic changes that are required for the mother to support optimal growth and development of her offspring during pregnancy. The levels of these hormones may provide a measurable indicator (biomarker) to help identify these at risk pregnancies. Levels of these hormones were measured in samples from week 20 of gestation from women who went on to have SGA babies and control pregnancies where babies were born at a size appropriate for gestation age. Despite the implications of prolactin and placental lactogen in maternal metabolism, no significant differences were detected suggesting that single measures of either prolactin or placental lactogen at 20 weeks gestation are unlikely to be useful biomarker to help detect SGA pregnancies.

Introduction: Parvalbumin (PV)-positive cells are strategic elements of neuronal networks capable of influencing memory and learning processes. However, it is not known whether pituitary hormones may be related to PV expression in the hippocampus – a part of the limbic system with important functions in learning and memory. Objective: Since previous studies indicate that prolactin (PRL) plays a significant role in hippocampal-dependent learning and synaptic plasticity, we hypothesized that a rise in PRL levels can modify PV expression in the hippocampus. Methods: We employed biochemical, immunohistochemistry, and densitometry techniques – as well as a behavioural assay – in a hyperprolactinemia model using subcutaneous osmotic pumps in female mice. Results: PRL treatment via osmotic pump induced an increase in PRL receptor (PRLR) expression in most regions of the hippocampus analysed by Western blotting and immunohistochemistry methods. Fluorescent densitometry analysis revealed that PV expression decreases in the same layers in the hippocampus following PRL treatment, while double labelling immunostaining indicated close localization of PV and PRLR in PV-positive interneurons. In addition, we found that PRL induced a reduction in the β2/3 subunit of GABAA receptor (GABAAR) expression that was linearly correlated with the reduction in PV expression. This reduction in the β2/3 subunit of GABAAR expression was maintained in trained animals in which PRL treatment improved the learning of a spatial memory task. Conclusions: These data show, for the first time, that an increase in PRL level is associated with changes in key constituent elements of inhibitory circuits in the hippocampus and may be of relevance for the alterations in cognitive function reported in hyperprolactinemia.

Objective Clozapine is the second-generation antipsychotic that induces the largest metabolic disorders. However, evidence is limited to the liabilities based on sex differences. This study aimed to investigate the effects of clozapine treatment on metabolic and neuroendocrine parameters, and the relationships between prescribed clozapine dosage and prolactin levels that may be associated with plasma clozapine concentrations, in 24 female and 24 male Japanese schizophrenia inpatients switched to clozapine. Methods Within female and male subjects, sequential changes in 7 items of metabolic parameters, including anthropometric measurements, fasting serum lipid components and glucose levels, and estimated insulin resistance at 2 months were evaluated and analyzed against clozapine dosages and prolactin levels at 2 months. Results Triglyceride levels, triglyceride to high-density lipoprotein ratios reflecting insulin resistance and glucose levels increased in female and male subjects. High-density lipoprotein cholesterol levels decreased in female and male subjects. High-density lipoprotein cholesterol levels were negatively correlated with prolactin levels in female subjects, and glucose levels were positively correlated with prolactin levels in male subjects, although clozapine doses showed no such correlations. Conclusions Clozapine administration developed sex-neutral metabolic disorders in the study subjects. Higher prolactin levels seemed to increase the risk of dyslipidemia and hyperglycemia with sex differences, which suggested that serum prolactin levels other than clozapine doses might be useful to predict sex-specific metabolic disorders. Further prospective studies, combining measurement of metabolic hormones and plasma concentrations of clozapine and its metabolites, will help to confirm our findings.

Context Human exposure to perfluoroalkyl substances (PFAS) has been associated with reduced duration of breastfeeding, although not consistently so, and mechanisms by which PFAS might affect breastfeeding are unknown. Objective To examine the association between early pregnancy serum-PFAS concentrations and breastfeeding termination and to elucidate the potential role of serum-prolactin concentrations in pregnancy. Materials and Methods Pregnant women from the Odense Child Cohort provided blood samples for analysis of 5 major PFAS (n = 1300) and prolactin concentrations (n = 924). They subsequently provided information about the duration of breastfeeding in questionnaires at 3 and 18 months postpartum, and a subgroup also provided breastfeeding information via weekly cell phone text messages. Associations between serum-PFAS concentrations and breastfeeding termination were analyzed using Cox regressions, while linear regression was used to assess associations between serum-PFAS and prolactin concentrations. Results Increased serum concentrations of perfluorooctane sulfonic acid, perfluorooctanoic acid, perfluorononanoic acid, and ∑PFAS were associated with a 16% (95% CI: 4%-30%), 14% (95% CI: 2%-26%), 14% (95% CI: 3%-27%), and 20% (95% CI: 6%-36%), respectively, increased risk of terminating breastfeeding at any given time after childbirth. Serum-PFAS concentrations were not associated with serum-prolactin concentrations. Conclusions These findings are of public health importance due to the global exposures to PFAS. Because breastfeeding is crucial to promote both child health and maternal health, adverse PFAS effects on the ability to breastfeed may have long-term health consequences.

What is known and objective Metformin was found to reduce elevated gonadotropin levels. The aim of the present study was to determine whether metformin modulates the impact of discontinuation of testosterone therapy on hypothalamic-pituitary-gonadal axis activity and sexual function in men with low testosterone levels. Methods The study included 28 men with late-onset hypogonadism (defined according to the criteria of the European Male Aging Study group) receiving testosterone undecanoate (120 mg in three equal doses), 12 of whom had been treated with oral metformin (1.7-3 g daily). Both testosterone and metformin had been administered for at least six months before enrolment. In all patients, testosterone replacement required to be discontinued. The control group included 16 testosterone- and metformin-treated men with late-onset hypogonadism who during the entire study period continued their treatment. Glucose homeostasis markers, as well as plasma levels of insulin, gonadotropins, testosterone, calculated bioavailable testosterone, dehydroepiandrosterone-sulphate, oestradiol, thyrotropin, free thyroxine, prolactin, insulin-growth factor-1 and cortisol were measured at the beginning of the study and four months later. Moreover, at the beginning and the end of the study, all enrolled patients completed a questionnaire assessing their sexual functioning (IIEF-15). Results and discussion Discontinuation of testosterone therapy resulted in a decrease in total testosterone and bioavailable testosterone (by 42% and 45% in metformin-treated patients, and by 52% and 54% in metformin-naive patients), as well as impaired all aspects of male sexual function. Changes in bioavailable testosterone, as well as in erectile function, orgasmic function and sexual desire were less pronounced if subjects received metformin. Only in metformin-naive men, follow-up FSH and LH levels were higher than at baseline (by 75% and 62%). Moreover, discontinuation of testosterone therapy in metformin-naive men increased glycated haemoglobin, as well as worsened insulin sensitivity. There were no differences between baseline and follow-up levels of the remaining hormones. In metformin-naive subjects, the increase in gonadotropin levels correlated with the changes in testosterone levels and insulin sensitivity. No effect on glucose homeostasis markers, hormone levels and sexual functioning was observed in the control group. What is new and conclusion The obtained results suggest that metformin treatment mitigates the unfavourable effect of discontinuation of testosterone treatment on hypothalamic-pituitary-testicular axis activity and sexual function in men with late-onset hypogonadism.

Background. The polycystic ovary syndrome (PCOS) is the most frequent form of endocrine pathology and occurs in 5–10 % women of reproductive age and makes up 80 %, and according to some data, even 90 % of all forms of hyperandrogenism. The information about pathogenesis of PCOS is contradictory. The main step of the SPCO pathogenesis is hyperproduction of LH of by the hypophysis, revealed in 40–80 % patients. According to one of numerous theories, an increase secretion results in the increase of LH by the hypothalamus of the gonadotropin-releasing hormone (GRH), secreted in the discrete mode under control sexual steroid hormones, monoamines and opioid peptides. The aim of the investigation is to study the functional status of hypophysis — gonads axis for women with SPCO. Material and methods. In the department of neuroendocrinology of the Center of Endocrinology of Health Ministry of the Republic of Uzbekistan in a period from September 2015 till July 2016 120 outpatients of fertile age with PCOS were inspected. Mean age of patients was 25.5 ± 4.3 years. The duration of the disease hesitated from 7 months to 9 years. 20 healthy women of corresponding age made a control group. The complex of researches, including clinical, biochemical (glycemia, glucose tolerance test), hormonal (LH, FSH, prolactin, estradiol, progesterone, dehydroepiandrostendion (ДGEA), 17-oxyprogesterone, аntimuller hormone (АМH), insulin) was performed in all patients, ultrasonic examination of uterus and ovaries (transabdominal and transvaginal) on the 14th day of cycle with folliculometria in dynamics, and also magnetically-resonant tomography of hypophysis and questionnaire of patients were carried out. Results. Patients were divided into two groups: with primary sterility (94 cases) and with secondary sterility (26 cases). In the first group of patients with primary sterility the reliable decline of both pituitary and ovarian hormones was determined on a background of hyperandrogenemia and hyperprolactinemia. So, as compared to the group of control on the 14th day of cycle LH, FSH, and estradiol, progesterone, while free testosterone, DGEA were enhanced as compared to control data. In the second group of patients the reliable decline of pituitary hormones was also educed on a background of hyperandrogenemia and hyperprolactinemia while an ovarian function was within the normal limits. So, as compared to the group of control on the 14th day of cycle the LH, FSH, here free testosterone, DGEA and АМH levels were enhanced as compared to control data. The neuroimaging of hypophysis in patients with PCOS educed hyperplasia (adenomatosis) of hypophysis in 49 from 120 (40.8 %), that can be explained by ovarian insufficiency in these patients. On the second place by incidence there was the syndrome of the empty sella (26 cases, 21.6 %), and on the third — the microadenoma of hypophysis in 16 persons (13.3 %). Conclusions. In the first group of patients with primary sterility the reliable decline of both pituitary and ovarian hormones was marked on a background of hyperandrogenemia and hyperprolactinemia. In the second group of patients the significant decline of pituitary hormones was also educed on a background of hyperanrogenemia and hyperprolactinemia, while an ovarian function was within the normal limits. In both groups of patients hypogonadotropinemia occurred combined with moderate hyperprolactinemia and hyperandrogenemia. Thus, the most expressed violations of the system of pituitary — ovarian function were found out in the first group of patients with PCOS with primary sterility, at that the significant decline of the functional status of pituitary — gonads axis was marked, namely decline of LH, FSH, estradiol and progesterone levels on the 14th day of menstrual cycle, that was confirmed by ultrasouns examination of uterus and ovaries by impoverishment of follicle vehicle of ovaries, anovulation signs. Thus, the most expressed violations of the system of pituitary-ovarial function were found out in the first group of patients with PCOS with primary sterility, at that the significant decline of the functional state of hypophysis-gonads was marked, namely decline of LH, FSH, estradiol and progesterone levels that was confirmed by ultrasound investigation of uterus and ovaries.

Background. Increase of morbidity of diabetes mellitus (DM) associated with coronary artery disease (CAD) on the background of metabolic syndrome (MS) is worrisome. It is very important to improve the diagnosis of this associated pathology and also to develop pathogenetic therapy, taking into account the specific stage of disease. The purpose of our work was to study the correlation of compensated and decompensated type 2 DM on the background of MS with chronic CAD. Materials and methods. 231 patients with MS and with or without type 2 DM and chronic CAD were examined. MS was characterized by the II–IIІ degree of obesity in all studied groups. The levels of cortisol, prolactin, free thyroxine, thyroid­stimulating hormone (TSH), lipids were evaluated in all patients, ultrasonography of the heart was performed. Results. Increase of cortisol levels, prolactin in women, TSH, change of lipids as high levels of triglycerides, very low­density lipoprotein cholesterol, at the control value of high­density lipoprotein cholesterol, low­density lipoprotein cholesterol and total cholesterol was detected in patients with metabolic syndrome, and also patients with compensated type 2 DM on the background of MS. Increase of interventricular septal thickness and left atrium anteroposterior dimension was observed in patients of this group. Increased levels of cortisol and prolactin as well as the control level of TSH were detected in patients with MS and decompensated type 2 DM as well as with or without chronic CAD. Increase of interventricular septal thickness, left ventricular posterior wall thickness, left atrium anteroposterior dimension was observed in patients of both groups according to results of ultrasonography. High level of total cholesterol, low­density lipoprotein cholesterol, triglycerides, very low­density lipoprotein cholesterol and low level of high­density lipoprotein cholesterol were observed in patients with MS and decompensated type 2 DM associated with chronic CAD compared to patients with MS and type 2 DM without chronic CAD. Conclusions. The pathogenetic and clinical relation of type 2 DM was established in MS and chronic CAD.

Idiopathic condylar resorption (ICR) is an aggressive form of temporomandibular joint disease that most frequently presents in adolescent girls during the pubertal growth spurt. Although numerous studies have indicated that the etiopathogenesis of ICR may be related to estrogen deficiency, the decisive role of estrogens remains controversial, and other sex hormone disturbances have not yet been investigated in this regard. Therefore, the aim of this study was to ascertain the role of serum estrogen levels and also the roles of other sex hormones in the pathogenesis of ICR. Ninety-four ICR patients and 324 disc displacement (DD) patients, of both sexes, were enrolled. Information on menstruation and serum levels of follicle-stimulating hormone, luteinizing hormone, prolactin, 17β-estradiol (E2), testosterone, and progesterone were recorded and analyzed. The results showed that female ICR patients had normal puberty onset, within the average age range. Use of oral contraceptives and other menstruation-regulating pharmaceuticals was similar in the two groups. Of note, neither serum E2 levels nor those of the other sex hormones differed significantly between female ICR and DD patients. However, male ICR patients had significantly increased serum testosterone levels (P=0.002) and relatively higher E2 levels (P=0.095) compared to DD patients. This study found that reduced serum E2 did not contribute to ICR; instead, systemic testosterone disturbances were found to be related to ICR.

Objective:This study aimed to evaluate the erectile function in patients undergoing dialysis due to chronic renal failure and ascertain the causes of erectile dysfunction (ED).Materials and Methods:Patients undergoing hemodialysis admitted to our outpatient clinic with an erectile function evaluation between February and August 2019 were retrospectively investigated. The International Index of Erectile Function form erection scores, hormone levels, total dialysis durations, libido, nocturnal erection, and other additional diseases were recorded.Results:A total of 28 patients had all mentioned values. The mean age of patients was 58.6 (35-75) years. In the study group, only two of all patients (7.14%) had no erection complaints and both of them were under 40 years old. Approximately 93% of patients had ED and ~79% of this patient group was over 50 years old. The dialysis duration of patients ranged between 8-180 months. Patients’ serum prolactin, glucose, testosterone, luteinizing hormone values, and erection scores were analyzed with Paired-Samples test. Glucose levels were found to be significant.Conclusion:The ED percentage is high, especially in patients over 50 years old with hemodialysis. The presence of diabetes in this patient group increased the erectile problems. Elevated prolactin alone was not detected as the cause of ED in patients undergoing dialysis. Further studies with larger series are necessary due to the limited number of patients in the study group; however, the current study suggested an investigation for ED in patients undergoing hemodialysis.

Soy isoflavones (SI) have strong estrogenic effect in tissues by binding to estrogen receptors and might be beneficial for women with polycystic ovarian syndrome (PCOS) by reduction in testosterone, cholesterol, insulin, weight gain, inflammatory markers, and oxidative stress. The study was planned to examine the effect of various levels of SI on nutrient intake, digestibility, lipid profile, insulin, and reproductive hormones of estradiol valerate (4 mg/rat/IM) PCOS induced rat models. Thirty‐six Wistar 45 days old rats weighing 95 ± 5 g were divided into 4 groups, each having 9 rats: C (control: without SF), SF10 (SF 0.10 g/kg BW), SF15 (SF 0.15 g/kg BW), and SF20 (SF 0.20 g/kg BW). SF was given through the oral gavage. Food and water were offered ad libitum, and intake was recorded daily. During last week of trial, collected feces by total collection method and blood samples were used to calculate nutrient digestibility and biochemical analysis, respectively. Estrogen, progesterone, and prolactin were (p, The objective of this study was to investigate the effect of different levels of soy isoflavones on blood insulin, lipid, and reproductive hormones profile of the female rats with PCOS.

Background: Generally, patients on hemodialysis for chronic renal failure also have endocrine defects and sexual function disorders. In this study, we aimed to assess the serum prolactin (PRL), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in patients with chronic renal failure. Methods: This hospital-based case–control study was conducted at Jabal Aulia Teaching Hospital, Khartoum, Sudan. The study was carried out between August 2019 and February 2020. A total of 100 subjects were enrolled – 50 chronic renal failure patients and 50 as controls. The serum hormones were estimated using Tosoh 360. SPSS version 25 was used to analyze the results. Results: The serum PRL, LH, and FSH were significantly increased among chronic renal failure patients than their healthy counterparts (p-value = 0.000). The age of patients was positive correlated with plasma hormones, PRL (r = 0.332, p = 0.001), LH (r = 0.387, p = 0.000), and FSH (r = 0.320, p = 0.001). No correlation was found between the duration of the disease and serum hormones. Conclusion: Patients with chronic renal failure had a highly significant increase of serum PRL, LH, and FSH and also the age of the patients was positively correlated with serum hormones. Keywords: chronic renal failure, prolactin, gonadotropin, hemodialysis

Background. Hyperprolactinemia can lead to negative cardiovascular events in patients with coronary heart di­sease and slow down the regeneration of the gastrointestinal tract mucous membrane. The purpose of the study was to determine the possible relationship between prolactin levels and the results of Holter electrocardiography (ECG) monitoring in patients with stable angina and gastroesophageal reflux disease (GERD). Materials and methods. The study included 118 patients with angina pectoris of I–II functional class. Of these, 88 patients with stable angina and comorbid GERD (A, B, C) were included in the second group, and 30 patients with isolated stable angina formed the first group. All patients who were included in the study prior to treatment were evaluated for serum prolactin levels and Holter ECG monitoring. Results. In patients with stable angina and GERD, prolactin levels exceed the norm and were higher than that of the group with isolated stable angina (p

Breastfeeding is a hallmark of mammals. The determination of the role of neuropeptides in the neuroendocrine regulation of mammary gland functions and parental behavior in mammals and humans is a priority for understanding these vital processes. Since in lactating females the suckling stimulus induces burst secretion of prolactin, oxytocin, and thyrotropin-releasing hormone (TRH), here we investigate the possibility of the effect of TRH on prolactin-dependent lactogenesis and oxytocin-mediated milk ejection reflex, as well as on components of the maternal behavior. It was found that bilateral intranasal infusions of TRH to lactating female mice specifically facilitate suckling, but not eating or drinking, behavior. TRH increased the duration of suckling periods and the number of milk ejection reflexes in response to pups’ sucking, while simultaneously increasing the duration of intervals in between. Optical and electron microscopic studies revealed significant alterations in mammary alveolar epitheliocytes, indicating a TRH-induced increase in milk production in the mammary gland, as confirmed by a higher rate of weight gain in mouse pups and their better survival. The absence of changes in females’ thyroxine and triiodothyronine plasma levels, as determined by enzyme immunoassay, after chronic infusions of low-dose TRH attests to the invariability of the maternal thyroid status. We assume that TRH is implicated in coordinating the mechanisms of patterning the neuroendocrine milk ejection reflex, maternal behavior, and increased synthetic activity in the mouse mammary gland.

© 2021 American College of Medical Genetics and GenomicsPurpose: We aimed to investigate the molecular basis underlying a novel phenotype including hypopituitarism associated with primary ovarian insufficiency. Methods: We used next-generation sequencing to identify variants in all pedigrees. Expression of Rnpc3/RNPC3 was analyzed by in situ hybridization on murine/human embryonic sections. CRISPR/Cas9 was used to generate mice carrying the p.Leu483Phe pathogenic variant in the conserved murine Rnpc3 RRM2 domain. Results: We described 15 patients from 9 pedigrees with biallelic pathogenic variants in RNPC3, encoding a specific protein component of the minor spliceosome, which is associated with a hypopituitary phenotype, including severe growth hormone (GH) deficiency, hypoprolactinemia, variable thyrotropin (also known as thyroid-stimulating hormone) deficiency, and anterior pituitary hypoplasia. Primary ovarian insufficiency was diagnosed in 8 of 9 affected females, whereas males had normal gonadal function. In addition, 2 affected males displayed normal growth when off GH treatment despite severe biochemical GH deficiency. In both mouse and human embryos, Rnpc3/RNPC3 was expressed in the developing forebrain, including the hypothalamus and Rathke's pouch. Female Rnpc3 mutant mice displayed a reduction in pituitary GH content but with no reproductive impairment in young mice. Male mice exhibited no obvious phenotype. Conclusion: Our findings suggest novel insights into the role of RNPC3 in female-specific gonadal function and emphasize a critical role for the minor spliceosome in pituitary and ovarian development and function.

Although pituitary adenomas (PAs) account for 15% of intracranial tumors, pituitary carcinomas (PCs) are a rare entity. Most commonly, PCs evolve from aggressive PAs invading the surrounding structures and eventually leading to metastatic lesions. Due to the low incidence, the diagnosis and treatment remains challenging. We report a case series of five patients with pituitary carcinoma (PC) treated in our center. At first diagnosis 3 patients had an ACTH-producing adenoma, 1 a prolactinoma and 1 a double secreting adenoma (GH and prolactin). The mean time interval from initial diagnosis to diagnosis of PC was 10.7 years (range 5-20 years). All patients underwent multiple surgical resections and radiotherapy. Four patients were treated with temozolomide for metastatic disease. One patient with concomitant radiochemotherapy for local recurrence. Temozolomide led to a stable disease in 2 patients. One patient had a progressive disease after 9 cycles of temozolomide. In absence of standard treatment, immunotherapy was initiated, resulting in a stable disease.We report five cases of PCs. Three patients obtained a stable disease after tailored multidisciplinary treatment. Additionally, one patient was treated with immunotherapy, opening a new treatment option in PCs. Overall, PCs are rare intracranial neoplasms occurring several years after the initial diagnosis of aggressive PAs. Currently, the absence of predictive factors for an aggressive clinical course, provokes a challenging management.

Background. Concomitant diseases due to a combination of metabolic and hormonal changes lead to the development of cardiovascular complications as a direct cause of death and reduced duration or quality of population’s life. The role of hormones in this combined pathology, especially their nosotropic and clinical relationship and correlation with the morphofunctional parameters of the myocardium, has not been studied thoroughly. It is difficult to analyse a lot of laboratory indexes in many comparison groups. The purpose is to set diagnostic markers in metabolic syndrome (MS) and also their relationship compared to combined pathology such as chronic coronary artery disease (CAD) and type 2 diabetes mellitus (DM). Materials and methods. Three hundred and nineteen patients were examined and divided into 6 groups: 82 people with metabolic syndrome were in the first group; 39 with compensated type 2 DM which developed as a result of МS — in the second group; 35 with DM and decompensated type 2 DM — in the third group; 44 individuals with МS complicated by CAD — in the fourth group; 44 with CAD and compensated type 2 DM which developed against the background of МS — in the fifth group; 75 with CAD and decompensated type 2 DM — in the sixth group. The control group consisted of 40 healthy individuals (17 men and 23 females). Then, the levels of prolactin, cortisol, free thyroxinе, thyroid-sti­mulating hormone, blood lipids were measured and cardiac ultrasonography was performed. An integral index for evaluating the significance of study results was used. It was calculated by the ratio of comparison group median to the control group median. The level ≥ 1.2 was set as a significance result. The sum of indexes (∑і) was calculated to describe changes in group indexes. Results. It is found that diagnosis of CAD objectively was not confirmed in female patients younger than 40 years with МS without type 2 DM with increased prolactin, cortisol, and thyroid-stimulating hormone. Thus, there already were initial changes of lipid exchange due to an increase in triglycerides and very low-density lipoprotein choleste­rol levels. Occurrence of CAD on the MS background (only in the absence of type 2 DM) is characterized by almost normal levels of prolactin and cortisol with significantly increased content of thyroid-stimulating hormone in all patients, regardless of gender. Me­tabolic disorders of blood lipids (increased triglycerides, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, total cholesterol, decreased high-density lipoprotein cholesterol), changes in the structural and functional state of the myocar­dium (increased left atrial anteroposterior dia­meter, left ventricular end-diastolic dimension, interventricular septal thickness and left ventricular posterior wall thickness) were observed in patients with CAD on the background of MS. Analysis of the correlation of ∑і of blood lipids, hormones with ultrasonography parameters found that in the 4th group of patients with CAD, the high value of blood lipid ∑і corresponds to the lowest ∑і of hormone indices. The 6th group of individuals with CAD combined with the decompensated type 2 DM is characterized by highest ∑і of both lipid exchange and hormones. The changes in the structural and functional state of myocardium are nonspeci­fic, more expressed with the combined pathology. In MS combined with CAD and compensated type 2 DM, the levels of hormones and lipids did not differ from those in MS with CAD without type 2 DM. There were increased levels of cortisol and prolactin with normal level of ТSH in MS complicated by decompensated type 2 DM and CAD. Analysis of blood lipids demonstrated increased levels of thyroid-stimulating hormone, triglycerides, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and decreased content of high-density lipoprotein cholesterol with significant ultrasonography changes as an increase in the left atrial anteroposterior diameter, left ventri­cular end-diastolic dimension, interventricular septal thickness, left ventricular posterior wall thickness and decreased ejection fraction. Conclusions. Diagnostic markers (hormone levels, blood lipid parameters and ultrasonographic changes in the myocardium) were determined in metabo­lic syndrome, and also their relationship was studied compared to combined pathology of CAD and type 2 DM.

Purpose: To determine the effect of Bu-Shen-Zhu-Yun Decoction (BSZY-D) on the kisspeptin through JAK2/STAT5 signaling pathway in hyperprolactinemia (HPRL) infertility. Method: SD rats were treated with BSZY-D for cerebrospinal fluid (CSF) extraction. GT1-7 cells were subjected to different treatments. The phosphorylation levels of JAK2 and STAT5, and the expressions of PRLR and kisspeptin of GT1-7 cells in different groups were detected by western blot, RT-qPCR and immunofluorescence. The expressions of CSN5 and GATA1 and other molecular features were checked by western blot, RT-PCR, co-immunoprecipitation and renilla luciferase activity. Results: The phosphorylation levels of JAK2 and STAT5, and the expressions of PRLR and kisspeptin in the HPRL group were significantly decreased, and these changes could be reversed after BSZY-D treatment. In addition, the presence of PRLR deubiquitination was detected in the HPRL group, which could be reversed by shRNA-CSN5, suggesting that BSZY-D played a role through targeting CSN5. The binding level of GATA1 and CSN5 promoter in the HPRL group was significantly decreased, but elevated in the HPRL (BSZY-D/CSF) group (P < 0.05). Conclusion: BSZY-D improved the transcription activity of GATA1 and increased the binding of GATA1 and CSN5. BSZY-D was involved in the deubiquitination of PRLR, which contributes to alleviating the symptoms of HPRL infertility.

BACKGROUND Aripiprazole is regarded as the first-line antipsychotic medication. Long-term aripiprazole therapy can cause hypoprolactinemia, which may result from its activity as a dopamine agonist. However, there is little information on hypoprolactinemia and steady-state aripiprazole concentrations. METHODS The subjects included 66 male and 177 female patients diagnosed with schizophrenia who were treated with aripiprazole. The plasma concentrations of aripiprazole and dehydroaripiprazole and the plasma concentration of prolactin were measured using high-performance liquid chromatography and enzyme immunoassay, respectively. A prolactin concentration of

Objective To determine the dose-dependent effect of contemporary marijuana exposure on female menstrual cyclicity and reproductive endocrine physiology in a nonhuman primate model. Design Research animal study. Setting Research institute environment. Animals Adult female rhesus macaques (6–12 years of age; n = 8). Intervention(s) Daily delta-9-tetrahydrocannabinol (THC) edible at medically and recreationally relevant contemporary doses. Main Outcome Measure(s) Menstrual cycle length (MCL), anti-Mullerian hormone, prolactin, basal follicle-stimulating hormone (FSH), estradiol (E2) and progesterone, luteinizing hormone (LH), and thyroid-stimulating hormone. Result(s) The average before THC weight was 6.9 kg (standard deviation, 0.8), and at the highest THC dosing, the average weight was 7.2 kg (standard deviation, 0.8). With increasing THC dosing, MCL and FSH concentrations increased, while basal E2 concentration was stable. The average MCL concentration increased 4.0 days for each mg/7 kg/day of THC (95% CI, 1.4–6.6 days). Follicle-stimulating hormone concentration increased significantly with increasing THC dose, 0.34 ng/mL for each mg/7 kg/day of THC (95% CI, 0.14–0.57 ng/mL). No significant trends were observed between THC dosing and average basal progesterone, anti-Mullerian hormone, prolactin, LH, or thyroid-stimulating hormone concentrations. Conclusion(s) In rhesus macaques, a dose response toward increased MCL and basal FSH concentrations but plateau of basal E2 and LH concentrations was observed with increasing THC dosing, suggesting ovulatory dysfunction. Further studies are needed to determine the effects of a longer duration of exposure and whether the significant increase in MCL and FSH concentrations results in reduced fecundity.

Background: Hyperprolactinemia is one of the most common hypothalamic-pituitary-endocrine disorders in women of reproductive age, with the highest frequency at the age of 25–44 years. In addition to influencing the reproductive system, it is important to study the effects of prolactin (PRL) on various metabolic links. Available data indicate that the effect of PRL on metabolism depends on its level. In this regard, the study of the relationship of different levels of PRL with anthropometric parameters, indicators of lipid and carbohydrate metabolism in young women is relevant.Aim: To study the frequency of metabolic syndrome (MS) and its individual components in women aged 25–45 years with different levels of prolactin.Materials and methods: Work design — cross-sectional research. A randompopulationsample of women 25–45 agedwas examined. Pregnant and breastfeeding women with macroprolactinoma, and taking antipsychotics were excluded. Information was collected using a structured ­questionnaire, including, but not limited to, the presence of pregnancies, childbirth, menstrual irregularities, and a clinical examination, anthropometric measurements, biochemical and hormonal blood analyzes were performed. Statistical data processing was carried out.Results: According to the inclusion and exclusion criteria, this analysis presents data from 401 women, the average age of the examibed was 36.14±6.19 years. There was no difference in the levels of thyroid-stimulating hormone and prolactin (PRL) in the age groups of 25–34 and 35–45 years. According to the survey, the incidence of thyroid diseases in the studied groups is comparable. Every fifth woman indicated menstrual irregularities. Among women 25–45 years old, women with low-normal PRL values (Me = 4.49 [3.52; 5.41] ng/ml) have more unfavorable metabolic indicators. Metabolic syndrome (MS) was detected in 28%,with a predominant increase in the frequency of abdominal obesity — 55%, hypercholesterolemic LDL — 63%. Women with high PRL (Me = 41.35 [34.78; 45.88] ng / ml) also have an unfavorable metabolic profile: MS was detected in 47%, abdominal obesity — 56%, hypertension — 39%.Conclusions: In women 25–45 years old, low and high PRL values are more often associated with metabolic ill health. PRL values are from 7.8 to 28 ng / ml, i.e. conditionally defined as normal, highly normal and at the level of moderate hyperprolactinemia contribute to the maintenance of a favorable metabolic profile. When deciding on the treatment of women with non-tumor etiology hyperprolactinemia, it is important to assess the metabolic status, expanding their understanding of PRL as a hormone associated only with lactation and with the pituitary-gonad axis.

Objectives To describe the case of a 12-year-old girl with a rare plurihormonal pituitary macroadenoma secreting prolactin (PRL), growth hormone (GH), thyroid-stimulating hormone (TSH), and alpha subunit (α-SU). Case presentation The patient experienced recurrent headaches and progressing loss of vision in one eye. During the examination, abnormalities such as tall stature, coarse facial features, enlarged feet and hands, tachycardia, hand tremor, hyperhidrosis, galactorrhea, and goiter were observed. Head magnetic resonance imaging (MRI) revealed a solid tumor in the anterior and middle cranial fossa, measuring 80 × 50 × 55 mm. A stereotactic biopsy revealed plurihormonal Pit-1 positive pituitary adenoma secreting PRL, GH, and TSH. A pituitary hyperfunction with PRL, GH, TSH, and α-SU excess was diagnosed. The patient was successfully treated pharmacologically with dopamine agonists and somatostatin analogue, and a decrease of tumor volume (30%) was achieved. Conclusions When neurosurgery is not possible, long-term pharmacological treatment of plurihormonal pituitary macroadenoma can be a safe and relatively effective alternative.

Background: Prolactin is synthesized in the ovaries and may play a role in ovarian cancer etiology. One prior prospective study observed a suggestive positive association between prolactin levels and risk of ovarian cancer. Methods: We conducted a pooled case–control study of 703 cases and 864 matched controls nested within five prospective cohorts. We used unconditional logistic regression to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between prolactin and ovarian cancer risk. We examined heterogeneity by menopausal status at blood collection, body mass index (BMI), age, and histotype. Results: Among women with known menopausal status, we observed a positive trend in the association between prolactin and ovarian cancer risk (Ptrend = 0.045; OR, quartile 4 vs. 1 = 1.34; 95% CI = 0.97–1.85), but no significant association was observed for premenopausal or postmenopausal women individually (corresponding OR = 1.38; 95% CI = 0.74–2.58; Ptrend = 0.32 and OR = 1.41; 95% CI = 0.93–2.13; Ptrend = 0.08, respectively; Pheterogeneity = 0.91). In stratified analyses, we observed a positive association between prolactin and risk for women with BMI ≥ 25 kg/m2, but not BMI < 25 kg/m2 (corresponding OR = 2.68; 95% CI = 1.56–4.59; Ptrend < 0.01 and OR = 0.90; 95% CI = 0.58–1.40; Ptrend = 0.98, respectively; Pheterogeneity < 0.01). Associations did not vary by age, postmenopausal hormone therapy use, histotype, or time between blood draw and diagnosis. Conclusions: We found a trend between higher prolactin levels and increased ovarian cancer risk, especially among women with a BMI ≥ 25 kg/m2. Impact: This work supports a previous study linking higher prolactin with ovarian carcinogenesis in a high adiposity setting. Future work is needed to understand the mechanism underlying this association.

OBJECTIVE To study the outcome of men with macroprolactinoma following cabergoline treatment based on tumour size. DESIGN Retrospective cohort study. METHODS The study included 94 men, divided into three groups according to adenoma diameter: 10-19 mm (Group A, n = 36); 20-39 mm (Group B, n = 41); or ≥40 mm (Group C, giant prolactinomas, n = 17). Patients were followed for a mean of 7.5 years with sellar magnetic resonance imaging, visual fields and hormone measurements. RESULTS Mean baseline prolactin was 767, 2090 and 24,806 ng/ml in Groups A, B and C, respectively (p

Introduction: Parkinson’s Disease (PD) associates with changes in sex hormones; however, it remains unknown whether this is either a cause for or a result of the disease. To further evaluate it, we investigated if the development of 6-Hydroxydopamine (6-OHDA)-induced Parkinsonism changes the serum levels of testosterone and prolactin or not. Methods: 6-OHDA was injected into the medial forebrain bundle using stereotaxic surgery. The development of Parkinsonism was evaluated by apomorphine-induced rotational test and the immunofluorescence labeling of Dopaminergic (DA) neurons in substantia nigra. The necessary blood samples were collected before the toxin and in the third and sixth weeks afterward. The hormones levels were determined using Enzyme-Linked Immunosorbent Assay (ELISA) kits. Results: The severity of rotations was different among 6-OHDA-treated rats; accordingly, they were divided into two subgroups of severe and mild parkinsonian rats. The degeneration of DA neurons was observed in both subgroups; however, it was significantly less in the mild group. In the sixth week after the toxin, testosterone level increased but only in the severe subgroup. Prolactin increased in both subgroups in the third week after the toxin but returned to normal in the sixth week. There was no association between the pre-toxin levels of these hormones and the intensity of Parkinsonism. Conclusion: Our findings indicated that the development of 6-OHDA-induced Parkinsonism increases the serum levels of testosterone and prolactin. Increased prolactin occurred earlier and was observed in rats with less DA neuronal loss. Therefore, prolactin levels can predict the death of DA neurons before the clinical signs of PD were revealed.

Kidney pathophysiology is influenced by gender. Evidence suggests that kidney damage is more severe in males than in females and that sexual hormones contribute to this. Elevated prolactin concentration is common in renal impairment patients and is associated with an unfavorable prognosis. However, PRL is involved in the osmoregulatory process and promotes endothelial proliferation, dilatation, and permeability in blood vessels. Several proteinases cleavage its structure, forming vasoinhibins. These fragments have antagonistic PRL effects on endothelium and might be associated with renal endothelial dysfunction, but its role in the kidneys has not been enough investigated. Therefore, the purpose of this review is to describe the influence of sexual dimorphism and gonadal hormones on kidney damage, emphasizing the role of the hormone prolactin and its cleavage products, the vasoinhibins.

Background POU1F1 encodes both PIT-1α, which plays pivotal roles in pituitary development and GH, PRL and TSHB expression, and the alternatively spliced isoform PIT-1β, which contains an insertion of 26-amino acids (β-domain) in the transactivation domain of PIT-1α due to the use of an alternative splice acceptor at the end of the first intron. PIT-1β is expressed at much lower levels than PIT-1α and represses endogenous PIT-1α transcriptional activity. Although POU1F1 mutations lead to combined pituitary hormone deficiency (CPHD), no patients with β-domain mutations have been reported. Results Here, we report that a three-generation family exhibited different degrees of CPHD, including growth hormone deficiency with intrafamilial variability of prolactin/TSH insufficiency and unexpected prolactinoma occurrence. The CPHD was due to a novel POU1F1 heterozygous variant (c.143-69T>G) in intron 1 of PIT-1α (RefSeq number NM_000306) or as c.152T>G (p.Ile51Ser) in exon 2 of PIT-1β (NM_001122757). Gene splicing experiments showed that this mutation yielded the PIT-1β transcript without other transcripts. The lymphocyte PIT-1β mRNA expression was significantly higher in the patients with the heterozygous mutation than a control. A luciferase reporter assay revealed that the PIT-1β-Ile51Ser mutant repressed PIT-1α and abolished transactivation capacity for the rat prolactin promoter in GH3 pituitary cells. Conclusions We describe, for the first time, that the PIT-1β mutation can cause CPHD through a novel genetic mechanism, such as PIT-1β overexpression, and that POU1F1 mutation might be associated with a prolactinoma. Analysis of new patients and long-term follow-up are needed to clarify the characteristics of PIT-1β mutations.

The aim of this trial was to evaluate the effects of an immunomodulatory supplement (OmniGen AF, OG; Phibro Animal Health Corp.) and heat stress on hormonal, inflammatory, and immunological responses of lactating dairy cows. Sixty multiparous Holstein cows were randomly assigned to 4 treatments in a 2 × 2 factorial arrangement using 2 environments: cooled using fans and misters, or noncooled, and 2 top-dressed feed supplements (56 g/d): OG or a placebo (CTL). Temperature-humidity index averaged 78 during the 8-wk trial. Blood was drawn to analyze cortisol, prolactin, and circulating tumor necrosis factor (TNF)-α and IL-10. Peripheral blood mononuclear cells (PBMC) were isolated and stimulated with hydrocortisone, prolactin, or lipopolysaccharide (LPS), individually or in several combinations, to assess induced proliferation and cytokine production. At d 52, 6 cows per treatment were injected i.v. with an LPS bolus (ivLPS) to assess hormone and cytokine responses. For cooled cows, feeding OG increased plasma cortisol concentration relative to CTL. Noncooled cows fed CTL had lower circulating TNF-α concentrations than noncooled-OG and cooled-CTL cows, with cooled-OG intermediate. Hydrocortisone+LPS-stimulated PBMC from OG cows tended to proliferate more than CTL. Relative to cooled cows, PBMC from noncooled cows produced more TNF-α and IL-10 when stimulated with LPS. Following ivLPS, cooled-OG cows had a greater cortisol response than the other treatments. In conclusion, OG supplementation enhanced cortisol release under basal condition and induced inflammation with cooling compared with CTL. This suggests that heat stress inhibits OG-mediated cortisol release. Heat stress seemed to enhance the inflammatory responses of PBMC from lactating cows. However, OG supplementation promoted PBMC proliferation under stress, or in the presence of hydrocortisone.

Despite most of the prolactinomas can be treated with endocrine therapy and/or surgery, a significant percentage of these tumors can be resistant to endocrine treatments and/or recur with prominent invasion into the surrounding anatomical structures. Hence, clinical, pathological, and molecular definitions of aggressive prolactinomas are important to guide for classical and novel treatment modalities. In this review, we aimed to define molecular endocrinological features of dopamine agonist-resistant and aggressive prolactinomas for designing future multimodality treatments. Besides surgery, temozolomide chemotherapy and radiotherapy, peptide receptor radionuclide therapy, estrogen pathway modulators, progesterone antagonists or agonists, mTOR/akt inhibitors, pasireotide, gefitinib/lapatinib, everolimus, and metformin are tested in preclinical models, anecdotal cases, and in small case series. Moreover, chorionic gonadotropin, gonadotropin releasing hormone, TGFβ and PRDM2 may seem like possible future targets for managing aggressive prolactinomas. Lastly, we discussed our management of a unique prolactinoma case by asking which tumors’ proliferative index (Ki67) increased from 5–6% to 26% in two subsequent surgeries performed in a 2-year period, exerted massive invasive growth, and secreted huge levels of prolactin leading up to levels of 1 605 671 ng/dl in blood.

Nicotine as a toxic agent in cigarette smoke impairs the reproductive system. Sambucus ebulus extract (SEE) is shown to have some beneficial effects such as antioxidant properties. The aim of this study was to evaluate the effects of SEE on the hormones of the pituitary-gonadal axis, lipid peroxidation index, antioxidant enzymes, spermatogenesis, and epididymal sperm parameters in male mice treated with nicotine. Adult male mice were divided into five groups; A: normal saline, B: 1 mg/kg nicotine, C: 1 mg/kg nicotine and 10 mg/kg SEE, D: 1 mg/kg nicotine and 50 mg/kg SEE, D: 1 mg/kg nicotine and 100 mg/kg SEE. Treatments lasted for 35 days. The spermicidal activity of SEE was tested in vitro. Sperm count, motility and morphology were assessed for fertility. Serum testosterone, prolactin and luteinizing hormone (LH) were measured, using ELISA. Serum malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) activity were measured, using colorimetric assays. Spermatogenesis was evaluated by Johnsen’s score and morphometry in histological slides. SEE at different doses did not have any spermicidal activity. Sperm parameters were reduced in the nicotine-treated group, compared with controls (P

Aim Several reports have shown that risperidone increases prolactin concentrations, while aripiprazole decreases prolactin concentrations. The frequency of abnormal prolactin concentrations in patients with schizophrenia receiving these drugs is still unknown. Furthermore, although hyperprolactinemia leads to sexual dysfunction, the relationship between hyperprolactinemia and testosterone, which may be directly related to male sexual function, is not well understood. Methods The subjects were 94 male schizophrenia outpatients receiving risperidone or paliperidone (risperidone group) and 83 male schizophrenia outpatients receiving aripiprazole. We measured the serum prolactin and total and free testosterone concentrations. We compared the prolactin and testosterone levels in patients receiving risperidone or paliperidone and patients receiving aripiprazole. Results The average serum prolactin concentration was 27.5 ± 13.1 ng/mL for the risperidone group and 3.9 ± 3.5 ng/mL for the aripiprazole group, and the concentrations were significantly different (P, There were very common hyperprolactinemia and hypoprolactinemia in the risperidone group and aripiprazole group, respectively. Free testosterone concentrations were associated with elevated prolactin levels in patients receiving risperidone or paliperidone.

Context Although gonadotropin-releasing hormone stimulation test (GnRHST) is the gold standard in diagnosing central precocious puberty (CPP), it is invasive, expensive, and time-consuming, requiring multiple blood samples to measure gonadotropin levels. Objective We evaluated whether urinary hormones could be potential biomarkers for prepuberty or postpuberty, aiming to simplify the current diagnosis and prognosis procedure. Methods We performed a cross-sectional study of a total of 355 girls with CPP in National Clinical Research Center for Child Health in China, including 258 girls with positive and 97 girls with negative results from GnRHST. Twenty patients received GnRH analogue (GnRHa) treatment and completed a 6-month follow up. We measured luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, prolactin, progesterone, testosterone, and human chorionic gonadotropin in the first morning voided urine samples. Results Their urinary LH levels and the ratios of LH to FSH increased significantly with the advancement in Tanner stages. uLH levels were positively associated with basal and peak LH levels in the serum after GnRH stimulation. A cutoff value of 1.74 IU/L for uLH reached a sensitivity of 69.4% and a specificity of 75.3% in predicting a positive GnRHST result. For the combined threshold (uLH ≥ 1.74 + uLH-to-uFSH ratio > 0.4), the specificity reached 86.6%. After 3 months of GnRHa therapy, the uLH and uFSH levels decreased accordingly. Conclusion uLH could be a reliable biomarker for initial CPP diagnosis and screening; uLH could also be an effective marker for evaluating the efficacy of clinical treatment.

Prolactin (PRL) is a pleiotropic hormone with a key role in pregnancy. In fetal membranes, PRL can regulate the secretion of pro-inflammatory factors, which induces the activation of matrix metalloproteinases (MMPs). The increase and activation of MMPs deregulate the turnover of the extracellular matrix in the fetal membranes, altering its structure and function, causing premature rupture of the membranes and preterm labor. In this work, we evaluate the effect of PRL upon the secretion of MMP-1, MMP-2, MMP-9, MMP-13, and the tissue inhibitors of metalloproteinases (TIMPs) in human fetal membranes after lipopolysaccharide (LPS) challenge. Nine fetal membranes from healthy non-laboring cesarean deliveries at term were cultured in a 2-independent chamber system and pre-treated with 250, 500, 1000 or 4000 ng/ml of PRL for 24 h, then choriodecidual region was stimulated with 500 ng/ml of LPS plus fresh PRL for 24 h. The MMPs and TIMPs secretion were quantified by ELISA, additionally MMP-2 and MMP-9 gelatinolytic activity was measured by zymography. LPS induced the MMP-9 and MMP-1 secretion, but no MMP-2 or MMP-13 in comparison with basal levels. PRL co-treatment decreased the MMP-2, MMP-9 and MMP-1 secretion induced by LPS. The active forms were present in the tissue extract, showing a response consistent with the secretion profile. TIMP-1 and TIMP-2 secretion was decreased after LPS treatment and the PRL co-treatment reverts this effect. The present results support that PRL may favor the balance between these factors involved in the structural maintenance of fetal membranes in an inflammatory event.

As a traditional veterinary medicine to promote lactation, Cui Nai Ling (CNL) can not only increase milk supply and promote health but also improve the overall physiological function and immunity of the animals. In order to further improve CNL’s effect on lactation, we have previously made a new CNL (NCNL) by adding Tetrapanacis Medulla and replacing Vaccariae Semen with fried Vaccariae Semen in CNL. We have demonstrated that the lactation-promoting effect of NCNL is better than that of CNL. However, the underlying mechanisms by which NCNL promotes lactation are unclear. In this study, we performed metabolomics, network pharmacology, and pharmacodynamic studies to explore the underlying mechanisms by which NCNL promotes lactation in rats with bromocriptine-induced hypogalactia. The results showed that NCNL significantly improved the loss of appetite in female adult rats and the weight loss of pups caused by the disorder of lactation. Biochemical analysis showed that NCNL could regulate the levels of PRL, T4, E2, Ca, UREA, GLU, ALT, AST, TCHO, and TG in serum. The pathological results showed that NCNL could promote lactation and increase the mammary gland index by improving breast acinar tissue morphology in rats with hypogalactia. Network pharmacology studies showed that NCNL promotes lactation through P13K-Akt, insulin resistance, and prolactin signaling pathways, among which the most frequently affected pathway was the P13K-Akt signaling pathway. Metabolomics studies showed that NCNL can significantly upregulate phenylalanine, tyrosine, and tryptophan biosynthesis and tyrosine metabolism pathways and downregulate cysteine and methionine metabolism pathways. NCNL can significantly increase the serum prolactin concentration, improve the glucose and lipid metabolism disorders, and regulate PI3K-Akt, insulin resistance, and prolactin pathways to affect the amino acids’ metabolism in the mammary gland and ultimately exert its therapeutic effect on bromocriptine-induced postpartum hypogalactia. These findings revealed the effect and application value of NCNL on animals with postpartum hypogalactia.

Context Cyproterone acetate (CPA) is a competitive inhibitor of the androgen receptor and exerts negative hypothalamic feedback. It is often used in combination with estrogens in trans women to achieve feminization. However, CPA has been associated with side effects such as changes in liver enzyme concentrations and increases in prolactin concentrations. The question is whether the testosterone-lowering effect, as well as these side effects, are dose dependent. Objective To assess the lowest effective dose of CPA in trans women to prevent side effects. Methods This longitudinal study, conducted at gender identity centers in Amsterdam, Ghent, and Florence, is part of the European Network for the Investigation of Gender Incongruence (ENIGI), a multicenter prospective cohort study. Participants were trans women (n = 882) using estrogens only or in combination with 10, 25, 50, or 100 mg CPA daily. The primary outcome measure was the concentration of testosterone at 3 and/or 12 months of hormone therapy. Results Using estrogens only (without CPA) led to testosterone concentrations of 5.5 nmol/L (standard error of the mean [SEM] 0.3). All doses of CPA resulted in testosterone concentrations below the predefined threshold of suppression of 2 nmol/L (10 mg, 0.9 nmol/L, SEM 0.7; 25 mg, 0.9 nmol/L, SEM 0.1; 50mg, 1.1 nmol/L, SEM 0.1; 100 mg, 0.9 nmol/L, SEM 0.7). Higher prolactin and lower high-density lipoprotein concentrations were observed with increasing doses of CPA. No differences in liver enzyme concentrations were found between the doses. Conclusion Compared with higher doses of CPA, a daily dose of 10 mg is equally effective in lowering testosterone concentrations in trans women, while showing fewer side effects.