Search

Si la 17-hydroxyprogestérone (17OHP) est historiquement le stéroïde dosé dans le dépistage et le diagnostic du déficit en 21-hydroxylase (CAH-21D), le profilage de sous-produits de la 11-hydroxylase, comme par exemple le métabolite strictement surrénalien 21-déoxycortisol (21DF), peut également être mesuré au cours de cette pathologie. Après le dépistage, et dans le contexte de la confirmation d’un CAH-21D, des facteurs confondants (tels que l’admission en unité de soins intensifs, le stress, la prématurité, le prélèvement précoce et les variations du développement du sexe [VDS]) peuvent interférer avec l’interprétation des biomarqueurs de référence (17OHP et 21DF). Dans une population de dépistés positifs pour le CAH-21D, le but de ce travail était de développer un nouveau panel de stéroïdes en spectrométrie de masse, plus sensible et plus spécifique. Ce panel, composé entre autres de sous-produits de la 11-hydroxylase, était appliqué sur le prélèvement de contrôle à l’étape de confirmation du diagnostic (au 9eou 10ejour de vie). La population étudiée comprenait 150 nouveau-nés, dont des cas de CAH-21D confirmés par biologie moléculaire, des CAH-21D non détectés et une population témoin de nouveau-nés atteints de cryptorchidie, d’hypospadias ou de VDS.

Dans le cancer de la prostate localisé, l’impact de l’hypogonadisme biochimique sur l’émergence et la progression du cancer est encore controversée. Notre objectif est de comparer les caractéristiques pathologiques et la récidive biologique (RB) à 5 ans après prostatectomie des patients atteints de cancer de la prostate (CaP) localisé en fonction du statut gonadique évalué par le total (TT) et la biodisponibilité (BT).

Cortisol and cortisone concentrations in serum and follicular fluid (FF) from women undergoing in-vitro fertilization (IVF) treatment were monitored. Four groups were included: group 1, women in their natural menstrual cycle having an endogenous mid-cycle surge of gonadotrophins; group 2, women in their natural menstrual cycle receiving human chorionic gonadotrophin (HCG) for ovulation induction; group 3, women receiving exogenous gonadotrophins for ovarian stimulation and HCG for ovulation induction; and group 4, women receiving exogenous gonadotrophins for ovarian stimulation, follicles being aspirated immediately before administration of HCG. In this study, 12 follicles contained oocytes which resulted in clinical pregnancy after IVF. Cortisone concentrations were significantly higher in FF compared with that of matched serum samples, while the opposite was observed for cortisol, resulting in cortisol:cortisone ratios being significantly lower in FF compared with serum. FF from group 4 showed significantly higher cortisone concentrations than FF from each of the other three groups. FF from group 1 showed significantly higher cortisone concentrations and significantly lower cortisol:cortisone ratios in comparison with groups 2 and 3. None of the observed parameters pinpointed any of the follicles containing oocytes which resulted in a clinical pregnancy. The intrafollicular concentrations of cortisol and cortisone suggest that pre-ovulatory follicles actively convert cortisol to cortisone. Neither FF concentrations of cortisol and cortisone nor the cortisol:cortisone ratio seem to reflect implantation potential of the derived pre-embryos.

Cortisol and cortisone concentrations in serum and follicular fluid (FF) from women undergoing in-vitro fertilization (IVF) treatment were monitored. Four groups were included: group 1, women in their natural menstrual cycle having an endogenous mid-cycle surge of gonadotrophins; group 2, women in their natural menstrual cycle receiving human chorionic gonadotrophin (HCG) for ovulation induction; group 3, women receiving exogenous gonadotrophins for ovarian stimulation and HCG for ovulation induction; and group 4, women receiving exogenous gonadotrophins for ovarian stimulation, follicles being aspirated immediately before administration of HCG. In this study, 12 follicles contained oocytes which resulted in clinical pregnancy after IVF. Cortisone concentrations were significantly higher in FF compared with that of matched serum samples, while the opposite was observed for cortisol, resulting in cortisol:cortisone ratios being significantly lower in FF compared with serum. FF from group 4 showed significantly higher cortisone concentrations than FF from each of the other three groups. FF from group 1 showed significantly higher cortisone concentrations and significantly lower cortisol:cortisone ratios in comparison with groups 2 and 3. None of the observed parameters pinpointed any of the follicles containing oocytes which resulted in a clinical pregnancy. The intrafollicular concentrations of cortisol and cortisone suggest that pre-ovulatory follicles actively convert cortisol to cortisone. Neither FF concentrations of cortisol and cortisone nor the cortisol:cortisone ratio seem to reflect implantation potential of the derived pre-embryos.

Cortisol and cortisone concentrations in serum and follicular fluid (FF) from women undergoing in-vitro fertilization (IVF) treatment were monitored. Four groups were included: group 1, women in their natural menstrual cycle having an endogenous mid-cycle surge of gonadotrophins; group 2, women in their natural menstrual cycle receiving human chorionic gonadotrophin (HCG) for ovulation induction; group 3, women receiving exogenous gonadotrophins for ovarian stimulation and HCG for ovulation induction; and group 4, women receiving exogenous gonadotrophins for ovarian stimulation, follicles being aspirated immediately before administration of HCG. In this study, 12 follicles contained oocytes which resulted in clinical pregnancy after IVF. Cortisone concentrations were significantly higher in FF compared with that of matched serum samples, while the opposite was observed for cortisol, resulting in cortisol:cortisone ratios being significantly lower in FF compared with serum. FF from group 4 showed significantly higher cortisone concentrations than FF from each of the other three groups. FF from group 1 showed significantly higher cortisone concentrations and significantly lower cortisol:cortisone ratios in comparison with groups 2 and 3. None of the observed parameters pinpointed any of the follicles containing oocytes which resulted in a clinical pregnancy. The intrafollicular concentrations of cortisol and cortisone suggest that pre-ovulatory follicles actively convert cortisol to cortisone. Neither FF concentrations of cortisol and cortisone nor the cortisol:cortisone ratio seem to reflect implantation potential of the derived pre-embryos.

AbstractBiotinylamidopropylammonium trifluoroacetate was obtained by acylation of 4-(tert-butyloxycarbonylamino)propylamine, followed by removal of the protective group. Consequently, it was found to be useful for the development of effective immunoassays.

OBJECTIVE: To evaluate insulin secretion and sensitivity in affected (diabetes mellitus or impaired glucose tolerance; n=7) and in unaffected (normal glucose tolerance; n=3) carriers of hepatocyte nuclear factor-1alpha (maturity-onset diabetes of the young-3 (MODY3)) gene mutations. METHODS: Insulin secretion was assessed by an i.v. glucose tolerance test (IVGTT), hyperglycemic clamp and arginine test, and insulin sensitivity by an euglycemic hyperinsulinemic clamp. Results were compared with those of diabetic MODY2 (glucokinase-deficient) and control subjects. RESULTS: The amount of insulin secreted during an IVGTT was decreased in affected MODY3 subjects (46+/-24 (s.d.) pmol/kg body weight (BW)) as compared with values in MODY2 (120+/-49pmol/kg BW) and control (173+/-37pmol/kg BW; P=0.0004) subjects. The amount of insulin secreted during a 10mmol/l glucose clamp was decreased in affected MODY3 subjects (171+/-78pmol/kg BW) and MODY2 subjects (302+/-104pmol/kg BW) as compared with control subjects (770+/-199pmol/kg BW; P=0.0001). Insulin secretion in response to arginine was decreased in affected MODY3 subjects. Milder and heterogeneous defects were observed in the unaffected MODY3 subjects; the amount of insulin secreted during the hyperglycemic clamp was 40-79% of that of controls. The response to arginine was abnormally delayed. Insulin sensitivity was decreased in diabetic but not in non-diabetic MODY3 subjects. CONCLUSIONS: Beta-cell dysfunction in response to glucose and arginine is observed in affected and unaffected MODY3 subjects. The MODY3 and MODY2 subtypes present different insulin secretion profiles. Secondary insulin resistance might contribute to the chronic hyperglycemia of MODY3 patients and modulate their glucose tolerance.

We report six women with severe acne lesions associated with taking amineptine, a tricyclic antidepressant. The lesions appeared after self-administration of high doses of the drug over long periods of time. They mainly occurred on the face, back, and thorax, but were also found on the extremities and in the perineal region. In five of the six cases, severity of cutaneous lesions appeared to be correlated with degree of overdose. The sixth patient never admitted having taken amineptine. Most of the patients had been unsuccessfully treated with isotretinoin for 18 months. In all six cases, chromatography of urinary 17-ketosteroids showed abnormal peaks and retention times which were different from those usually found for known steroids. In addition, the areas under these peaks were found to be a function of the degree of intoxication and of the clinical severity of the lesions. Mass spectrometry was used to qualitatively study urinary amineptine metabolites, disclosing compounds normally found only in trace amounts, as well as certain others heretofore not described in man. In two of the three patients who stopped taking amineptine, cutaneous lesions subsequently diminished, totally disappearing in the least severe case.

This study showed that endothelins (ETs) stimulate DNA and proteoglycan synthesis in monolayer culture of rat articular chondrocytes (AC) by interacting with specific cell surface receptors. The high affinity receptors bound [125I]ET-1 with aKdof 0.54 nM and Bmaxof 81.4 pM/μg DNA (approximately 40 000 binding sites per cell) was demonstrated. [125I]ET-1 binding was completely inhibited by unlabelled ET-1 or ET-2, and by BQ123 (ETAreceptor antagonist), whereas ET-3 and IRL1038 (ETBreceptor antagonist) did so only weakly. SDS-PAGE of cell extracts containing [125I]ET-1 cross-linked to the receptors, followed by autoradiography of the gels revealed a single 50-kDa band. These findings indicate that most of the receptors are subtype ETA. Although mRNA transcripts specific for both ETAand ETBreceptors were found by RT-PCR, the ETAmRNA was more abundant. ET-1 increased the production of cAMP, cGMP and prostaglandin E2(PGE2) and protein kinase C (PKC) activity in a concentration- and time-dependent manner. ET-1, and to a lesser degree ET-2, stimulated DNA synthesis, whereas ET-3 was inactive. Stimulation of DNA synthesis by ET-1 was strongly inhibited in a concentration-dependent manner by BQ123 and, to a much lesser degree, by IRL1038, which is consistent with an ETAreceptor. ET-1 also stimulated proteoglycan synthesis and increased the amount of mRNA specific for the aggrecan gene. These findings strongly suggest that ET-1 is involved in regulating chondrocyte proliferation and metabolism in health, and presumably in disease.

Plasma adrenocorticotrophin (ACTH) and cortisol (F) concentrations were studied in six male subjects under normoxic (N) and acute hypoxic (H) conditions (altitude 3000 m) in a hypobaric chamber. Comparisons were made at rest, at 15, 30, and 60 min of exercise (65% $$\dot V_{{\text{O}}_{{\text{2max}}} } $$ ), and after a 10 min recovery period. Mean (±SE) resting plasma ACTH levels were significantly higher in H (18.6±5.7 pmol · l-1) than in N (9.6±1.6 pmol · l-1) but no difference in resting plasma cortisol was observed between the two conditions. Both plasma ACTH and F concentrations were significantly increased at 60 min of exercise and during the recovery period under normoxic conditions. Hypoxia did not affect the ACTH response to exercise but reduced cortisol elevation. The changes in plasma cortisol concentration from rest to exercise were significantly correlated to ACTH under normoxic (r=0.89,p<0.001) but not under hypoxic (r=0.43, NS) conditions. Plasma lactate concentration was higher at the end of exercise in hypoxia (p<0.01), and no correlation existed between plasma lactate and ACTH levels. These observations provide further evidence that at sea level the increase in plasma cortisol levels during exercise is the result of ACTH-induced steroidogenesis. The responses observed at rest and during exercise in hypoxia suggest that adrenal sensitivity for ACTH may be altered.

Abstract. Using a highly specific radioimmunoassay recently described, plasma 21-deoxycortisol levels were measured in 55 heterozygous carriers of 21-hydroxylase deficiency (as demonstrated by HLA typing). Mean baseline 21-deoxycortisol levels were above the normal range, but there was a 38% overlap with control values. In contrast to 17-hydroxyprogesterone levels, which in 71% of the subjects remained within the normal range one hour after ACTH stimulation, 21-deoxycortisol levels increased over stimulated control levels in all but two heterozygous carriers. No differences as to the levels were observed between heterozygous carriers for the classic and the late-onset forms. Plasma 21-deoxycortisol measurement appears to be a valid tool in the biological detection of heterozygosity for 21-hydroxylase deficiency and its implications in genetic counselling.

All androgen-sensitive peripheral tissues and cells, including the prostate, are commonly believed to possess the ability to metabolize testosterone. We report on the in vitro metabolism of tritiated testosterone performed in immortalized human adult normal prostatic epithelial cells and in human adult normal prostate fibroblastic cells (stromal cells). These two cell types were incubated separately with increasing testosterone concentrations (1 to 50nM.) for 2 and 4hours, after which the testosterone metabolic profile was analyzed. Data analysis provided evidence, for the first time, of the existence of two different 5a-reduced metabolic pathways. Stromal cells preferred the androsterone pathway via the oxidative androstenedione formation, whereas epithelial cells preferred the reductive 5a-dihydrotestosterone pathway. These two 5a-reduced metabolites were produced in nearly equal quantities regardless of testosterone concentration or time of incubation. Since interactions between epithelial and stromal cells are involved in the development of the prostate, the availability of defined epithelial and stromal cells suitable for in vitro experiments provides a useful tool for the study of the contribution of androgens to these interactions. The model presented in this study would permit a better evaluation of the intraprostatic regulation of androgen metabolism and the contribution of the anti-5a-reductase drugs to the management of benign prostate hyperplasia.

In 10 patients, 8 males and 2 females, suffering from idiopathic hemochromatosis (IH), the gonadotropic function has been studied using the GnRH test (iv administration of 100 μg) to make precise the pathogenesis of their hypogonadism. The FSH and LH mean basal levels were low and almost unaffected by GnRH (p< 0.001 at each time value when compared to controls). The hypogonadism often observed during the course of IH seems to be hypogonadotropic. Various factors could be responsible for this disturbance. The exact site of the lesion, whether hypothalamic or hypophyseal, remains unknown.

We report the effects of sublingual absorption of a single dose (0.5 mg) of oestradiol-17β (E2) in 8 post-menopausal women, on plasma E2and oestrone (E1), urine elimination of total E2+ E1and on plasma FSH and LH.The results show that sublingual absorption of E2occurs and that plasma concentrations of E2obtained (between 133.2 to 320 pmol/1) in this way were higher than those obtained after percutaneous absorption of a single dose (3 mg)of E2.The ratio E1/E2in plasma is close to that of pre-menopausal women.

Approximately 50 percent of all malignant prostatic tumors contain neuroendocrine cells, which cannot be attributed to small cell prostatic carcinoma or carcinoid-like tumors, and which represent only 1 to 2 percent of all prostatic malignancies. Only limited data are available concerning the plasma levels of neuroendocrine markers in patients with prostatic tumors. Therefore, we determined the incidence of high plasma levels of neuroendocrine markers in patients with benign and malignant prostatic disease.

Recent reports have shown that RU 486, a synthetic glucocorticoid and progestin antagonist, has direct effects on tissues secreting steroids. In order to characterize the effects of RU 486 on steroidogenesis further, guinea-pig fasciculata-glomerulosa (FG) cells in primary culture were treated for 48 h with RU 486. RU 486 caused an alteration of basal as well as ACTH-stimulated steroid secretion. Corticosterone and cortisol secretion decreased by 50% while the secretion of 17-hydroxyprogesterone and C19steroids were increased. The activity of steroidogenic enzymes was measured using tritiated steroids. In RU 486-treated cells, the activity of 21-hydroxylase was dramatically inhibited while there was an increase in 17-hydroxylase and 17,20-desmolase activities. The effects of RU 486 on enzyme activities were dependent upon dose and time. The effects of the compound were not reversed by concomitant treatment of FG cells with R-5020 or dexamethasone, thus suggesting that RU 486 acted directly on steroidogenic enzymes to alter their activity.Journal of Endocrinology(1991) 130,71–78

Abstract. A radioimmunoassay for 21-deoxycortisol is described. The immunogen, 21-deoxycortisol-3-(O-carboxymethyl) oxime-bovine serum albumin, was prepared, the antisera raised against it were studied and the reliability of the assay was checked. The antiserum selected cross-reacted with 11-deoxycortisol (0.08%), corticosterone (0.25%), cortisol (0.6%) and 17-hydroxyprogesterone (1.6%). 21-deoxycortisol was separated by celite partition chromatography and eluted in the 70/30 (v/v) isooctane/ethyl acetate fraction together with 11-deoxycortisol and corticosterone.The radioimmunoassay was used to measure 21-deoxycortisol in the plasma of normal subjects and patients with androgen excess. In normal subjects, men (0.19 ng/ml ± 0.08) and women (0.18 ng/ml ± 0.09) had similar basal levels (mean ± sd). One hour after ACTH stimulation, these levels were increased by a factor of 3.5. In 7 patients treated for classical congenital adrenal hyperplasia associated with 21-hydroxylase deficiency, basal values varied between 9.1 and 39.9 ng/ml (measured at 8 a.m.). In 7 untreated women with lateonset congenital adrenal hyperplasia (with 21-hydroxylase deficiency), ACTH-stimulated levels were increased to between 9 and 25.5 ng/ml. In 14 heterozygous carriers of 21-hydroxylase deficiency, diagnosed by HLA genotyping, all ACTH-stimulated levels were well above the highest corresponding levels in normal subjects, whereas 17-hydroxyprogesterone levels remained within the normal range in 9 of the cases.

Abstract. A 25 year old man presented hypogonadotropic hypogonadism with complete anosmia (Kallman's syndrome). His chromosomic type was 47 XXY (Klinefelter's syndrome). Clinical findings were: height 183 cm, weight 62 kg, increased length of lower limbs, P2–A2 pilosity and micropenis. Only a left testis was present (1.5–1.5 cm). Bone age was 15. Testicular biopsy showed that the signs were more related to the gonadotropic deficit than to the gonadal dysgenesis; tubular hyalinization was not observed. Plasma levels of testosterone and oestradiol were very low. Plasma gonadotropin levels were below normal ranges and did not respond to an infusion test of GnRH. GnRH was administrated iv every 90 min for 3 weeks by an auto syringe infusion pump and induced a pulsatile response of FSH and LH. Plasma levels of testosterone and oestradiol were unaffected. It may be concluded that the results of pulsatile injection of GnRH confirmed in this patient a unique association of Kallmann's syndrome with complete 47 XXY Klinefelter's syndrome.

Les concentrations intraprostatique des stéroïdes sexuels et leurs corrélations aux concentration sériques ont fait l’objet d’études parcellaire avec des méthodologies de dosage critiquables. L’objectif de l’essais STERPROSER a été rechercher des différences dans les concentrations des stéroïdes sexuels dans le plasma et des échantillons chirurgicaux frais de prostate centrale bénigne selon le volume de la prostate.

Dans le cancer localisé de la prostate (PCa), l’impact de l’hypogonadisme biochimique sur l’émergence du cancer et la progression est encore controversé. Nous avons comparé les profils sériques préopératoires des hormones sexuelles et les caractéristiques pathologiques chez les patients atteints de PCa localisés selon leur statut gonadique évalué par la testostéronémie totale (TT) et biodisponible (BT).

Actuellement, il n’existe pas de références sur les concentrations d’androgènes intratissulaires prostatiques attendues chez les patients atteints de cancer de prostate. Notre objectif était de comparer les concentrations sériques et intraprostatiques des stéroïdes sexuels, auprès de patients atteints de cancer de prostate (CAP) ou d’hypertrophie bénigne de prostate (HBP).

Dans le cancer localisé de la prostate (PCa), l’impact des concentrations des stéroïdes sexuels sur l’agressivité du cancer est débattu, certains auteurs rapportant une association à la testostéronémie totale (TT), biodisponible (BT) ou à l’estradiol (E2). Nous avons comparé les profils sériques préopératoires des hormones sexuelles et les caractéristiques pathologiques chez les patients atteints de PCa localisés selon la prédominance du grade de Gleason 4 sur la pièce de prostatectomie.

Développer un profil stéroïdien quantitatif par spectrométrie de masse pour l’étude des déficits enzymatiques surrénaliens (DES) et ainsi substituer la LC-MS/MS aux approches analytiques de RIA.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Plasma 21-deoxycortisol (21 DF) was measured by using an anti-serum raised in the rabbit with 21-deoxycortisol-3-0-carboxymethyl oxime-BSA. This anti-serum cross-reacted with 11-deoxycortisol (0.08%), corticosterone (0.35%), cortisol (0.6%) and 17-hydroxyprogesterone (1.6%). 21 DF was separated by celite partition chromatography and was eluted in the fraction isooctane 70v/ethylacetate 30v, together with 11-deoxycortisol and corticosterone. In 38 healthy volunteers (16 men and 22 women) 21 DF mean basal value was 166 pg/ml at 8 a.m. with a range of 66 - 401 pg/ml. After a Synacthen test, performed in 14 subjects, the maximum mean level was 414 pg/ml (151-930). In 31 congenital adrenal hyperplasia family members heterozygous for 21-hydroxylase deficiency proved by HLA genotyping, 21 DF mean basal level was 323 pg/ml (50-1,380). After Synacthen it increased up to 2,380 (1,070-9,060). In contrast with 17-hydroxyprogesterone which was also measured and which remained in the normal range after Synacthen in 12 cases out of the 31 , 21 DF under stimulation increased to pathological levels in all the cases studied. Therefore we believe that plasma 21 DF measurement could be of great interest in the biological detection of heterezygous subjects for 21-hydroxylase deficiency.