Biomedical subjects

J Fiet

Publications and source records attributed to J Fiet.

At least 55 records · Page 3Linked to original sources

PubMed1997

[A case of apparent mineralocorticoid excess caused by type 2 11 beta- hydroxysteroid dehydrogenase deficiency].

The syndrome of apparent mineralocorticoid excess is a recessively inherited form of low renin hypertension. The syndrome is characterised by sodium retention and hypervolemia despite low plasma renin activity and aldosterone levels. Patients with this syndrome have mutations in the 11HSD2 gene which encodes the enzyme which normally converts cortisol in the renal tubule to its inactive form, cortisone. The unconverted cortisol is thus able to bind and activate the mineralocorticoid receptor, displacing its usual ligand, aldosterone, causing the apparent mineralocorticoid excess. We have studied a patient with severe hypertension, low renin and aldosterone, and a chronic hypokalemic alkalosis at age 4. The analysis of cortisone, cortisol and their metabolites showed the specific pattern of the apparent mineralocorticoid excess. In serum and urine, there was a dramatic decrease of cortisone and its metabolite, while cortisol and its metabolites were non affected.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1996

Identification of endothelin receptors in normal and hyperplasic human prostate tissues.

Specific endothelin-1 (ET1) binding sites have been demonstrated in membranes derived form normal (NP) and benign hyperplasic (BPH) human prostate using an 125I-ET1 binding assay. 125I saturation experiments and Scatchard analysis demonstrated the existence of a homogeneous population of binding sites with high affinity (Kd(app)) and density (B(max)), respectively, 106 +/- 15 pM and 1086 +/- 399 fmol/mg protein for NP (n = 5) and 168 +/- 26 pM and 964 +/- 445 fmol/mg protein for BPH (n = 5). We demonstrated the presence of two subtypes of ET1 receptors, ETA and ETB, by means of the following ET1 competitors: ET2, ET3, and BQ123 (which is selective for the ETA receptor), and IRL1620 and sarafotoxine c (S6c) (which are selective for the ETB receptor). The displacement curves allowed us to conclude that the large majority (85%) of the ET1 receptors in normal and hyperplasic human prostate are of the A subtype.

Binding, Competitive↗

PubMed1996

Establishment of permanent human endothelial cells achieved by transfection with SV40 large T antigen that retain typical phenotypical and functional characteristics.

The plasmid pMK16 containing-SV40 replicated origin defective gene was efficiently introduced into early-passage human umbilical vein endothelial cells (HUVEC) using positively charged liposomes. The resulting cell line acquired an almost infinite lifespan, was morphologically unchanged, expressed SV40-antigen, and coexpressed von Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), angiotensin conversion enzyme (ACE), and endothelin converting enzyme (ECE). In addition, these are the first immortalized human endothelial cells, to our knowledge, that biosynthesized and secreted interleukins (IL-1 beta and IL-6) in both a constitutive and regulated fashion and endothelin-1 (ET-1), the most potent vasoactive peptide, which has been suggested to be implicated in the pathogenesis of hypertension. Interestingly enough, both of the immortalized cells and the early-passage HUVEC from which the immortalized cells were obtained biosynthesized and secreted the same levels of ET-1 suggesting full maintenance of its biosynthetic pathway including the presence of active ECE, which cleaves big endothelin-1 (big-ET-1) to ET-1 and regulation factors. Moreover, the immortalized cells retained the ability to express the functional specific amino acid Na(+)-independent system Y+ transporter, which mediates L-arginine transport into endothelial cells from which endothelium-derived relaxing factor (EDRF, nitric oxide) is formed via the action of nitric oxide-synthase. Obtaining these immortalized human endothelial cells without alteration of the differentiated characteristics constitutes a useful model: (a) to study ET-1 secretion, gene regulation, and human ECE, which may be an important therapeutic target in disease conditions in which ET-1 is to be implicated; (b) to study L-arginine transport, which is a key step in the formation of EDRF; (c) to study IL-1 beta and IL-6 secretions, and gene regulations; (d) to substitute large quantities of HUVEC; and, finally, (e) to reproduce, starting with different primary endothelial cells both from human and animal origin.

Antigens, Polyomavirus Transforming↗

PubMed1996

11 beta-Hydroxysteroid dehydrogenase deficit: a rare cause of arterial Hypertension. Diagnosis and therapeutic approach in two young brothers.

We report the clinical history and results of endocrine investigations in two brothers born to consanguineous parents, who presented with hypokalemia and arterial hypertension when they were aged 2 and 6 years. The hormonal serum assay results, including extremely low values for aldosterone and plasma renin activity, favored the existence of apparent mineralocorticoid excess. A diagnosis of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) deficiency was made, based on assays of the hydrogenated urinary metabolites of cortisol and cortisone, as well as of corticosterone and dehydrocorticosterone. Indeed we found a very low rate of urinary elimination of cortisone metabolites: tetrahydrogenated cortisone was reduced to between 0.10 and 30 mumol/24 h, which is 15-100 times lower than the normal rate; hexahydrogenated cortolones alpha and beta were found to be 7- to 20-fold lower than normal levels; and the 11-keto-17-ketosteroid derivatives of cortisone were also reduced. Urinary elimination of the cortisol-reduced metabolites 5 beta- and 5 alpha-tetrahydrogenated cortisol were slightly reduced or normal. These results argue in favor of a deficit in the enzyme 11 beta-HSD, which oxidizes cortisol into cortisone. A moderate defect in the conversion of cortisol into 5 beta-THF compared to normal conversion into 5 alpha-THF was also found. With respect to corticosterone metabolism, we demonstrated the presence of a defect in the oxidation of that steroid into dehydrocorticosterone, also due to the deficit in 11 beta-HSD. Arterial hypertension and hypokalemia were corrected by treatment with dexamethasone, concomitantly with correction of the low aldosterone and plasma renin activity levels. On the other hand, during this treatment, urinary concentrations of the metabolites of cortisol, cortisone and corticosterone were only moderately affected.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1996

Clinical phenotypes, insulin secretion, and insulin sensitivity in kindreds with maternally inherited diabetes and deafness due to mitochondrial tRNALeu(UUR) gene mutation.

An A-to-G transition in the mitochondrial tRNALeu(UUR) gene at base pair 3243 has been shown to be associated with the maternally transmitted clinical phenotype of NIDDM and sensorineural hearing loss in white and Japanese pedigrees. We have detected this mutation in 25 of 50 tested members of five white French pedigrees. Affected (mutation-positive) family members presented variable clinical features, ranging from normal glucose tolerance (NGT) to insulin-requiring diabetes. The present report describes the clinical phenotypes of affected members and detailed evaluations of insulin secretion and insulin sensitivity in seven mutation-positive individuals who have a range of glucose tolerance from normal (n = 3) to impaired (n = 1) to NIDDM (n = 3). Insulin secretion was evaluated during two experimental protocols: the first involved the measurement of insulin secretory responses during intravenous glucose tolerance test, hyperglycemic clamp, and intravenous injection of arginine. The second consisted of the administration of graded and oscillatory infusions of glucose and studies to define C-peptide kinetics. This protocol was aimed at assessing two sensitive measures of beta-cell dysfunction: the priming effect of glucose on the glucose-insulin secretion rate (ISR) dose-response curve and the ability of oscillatory glucose infusion to entrain insulin secretory oscillations. Insulin sensitivity was assessed by euglycemic-hyperinsulinemic clamp. Evaluation of insulin secretion demonstrated a large degree of between- and within-subject variability. However, all subjects, including those with NGT, demonstrated abnormal insulin secretion on at least one of the tests. In the four subjects with normal or impaired glucose tolerance, glucose failed to prime the ISR response, entrainment of ultradian insulin secretory oscillations was abnormal, or both defects were present. The response to arginine was always preserved, including in subjects with NIDDM. Insulin resistance was observed only in the subjects with overt diabetes. In conclusion, the pathophysiological mechanisms responsible for the development of NIDDM and insulin-requiring diabetes in this syndrome are complex and might include defects in insulin production, glucose toxicity, and insulin resistance. However, our data suggest that a defect of glucose-regulated insulin secretion is an early possible primary abnormality in carriers of the mutation. This defect might result from the progressive reduction of oxidative phosphorylation and implicate the glucose-sensing mechanism of beta-cells.

Adenine↗

PubMed1996

Argon laser induced autofluorescence may distinguish between normal and tumor human urothelial cells: a microspectrofluorimetric study.

PURPOSE: To assess the ability of argon laser-induced autofluorescence spectroscopy (LIAFS) to discriminate normal from tumor human urothelial cells. MATERIALS AND METHODS: Emission spectra of single living cells excited at 488 nm. have been studied with confocal microspectrofluorimeter. RESULTS: Cellular autofluorescence appeared as a broad band with a maximum in the same "green" spectral range, 550 to 560 nm., probably corresponding to oxidized flavoprotein emission. However, the maximum autofluorescence intensity of normal urothelial cells was much higher, 10 times (p<0.0001) that of any of the tumor cell types tested. CONCLUSIONS: These results, suggesting a significantly reduced oxidized flavoprotein concentration in tumor urothelial cells, should prompt us to evaluate argon LIAFS as a potential tool to detect occult urothelial severe dysplasia and carcinoma in situ.

Argon↗

PubMed1996

Plasma neuroendocrine markers in patients with benign prostatic hyperplasia and prostatic carcinoma.

PURPOSE: Approximately 50% 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% of all prostatic malignancies. Only limited data are available concerning the plasma levels of neuroendocrine markers in patients with prostatic tumors. Therefore, we determine the incidence of high plasma levels of neuroendocrine markers in patients with benign and malignant prostatic disease. MATERIALS AND METHODS: The presence of elevated plasma neuropeptide levels was investigated in 135 patients with prostatic carcinoma and 28 with benign prostatic hyperplasia. Plasma chromogranin A, neurone-specific enolase, substance P, calcitonin, somatostatin, neurotensin and bombesin levels were analyzed by immunoassays, and were compared to clinical and pathological stages of disease. Plasma prostatic acid phosphatase and prostate specific antigen levels were also determined. All patients were followed for at least 2 years after inclusion in the study. RESULTS: Significantly elevated levels of chromogranin A were detected in 15% of patients with prostatic carcinoma before any treatment. During hormone resistant prostate cancer progression plasma chromogranin A and neuron-specific enolase levels were elevated in 55% and 30% of the patients, respectively. In patients with stage D3 disease survival curves were generated by the Kaplan-Meier method, and log rank analysis revealed a statistically significant difference between groups positive and negative for chromogranin A. Substance P and bombesin were also occasionally elevated in prostatic tumors. Determination of neuroendocrine differentiation by neuron-specific enolase or chromogranin A immunoassays was not helpful in the prediction of progressive localized prostatic carcinoma. CONCLUSIONS: Future studies of plasma neuropeptide levels should confirm whether these parameters can be used as prognostic markers during late progression of prostatic carcinoma or for the selection of patients suitable for evaluation of new antineoplastic drugs to be active against neuroendocrine tumors.

Acid Phosphatase↗

PubMed1995

A simple synthesis of 11,19-oxidosteroids.

The photochemical hypoiodination of cortisol acetonide gave a mixture of 18-iodocortisol acetonide and of the 11 beta,19-oxidoderivative. The proportion of the two products was slightly modified by the reaction temperature. Deprotection of the acetonide group of the 11 beta,19-oxidoderivative gave 11 beta,19-oxido-17 alpha,21-dihydroxy-4-pregnen-3,20-dione which led to the formation of 11 beta,19-oxido-4-androsten-3,17-dione upon treatment with sodium bismutate.

Androstenedione↗

PubMed1995

17 beta-Estradiol: oral or parenteral administration in hyperandrogenic women? Metabolic tolerance in association with cyproterone acetate.

OBJECTIVE: To compare the metabolic effects of two different administration routes of estrogen associated with cyproterone acetate (CPA) in young women. DESIGN: Randomized and prospective study. SETTING: University medical and research center. PATIENTS: Sixty-five premenopausal young women with clinical hyperandrogenism. INTERVENTIONS: A high dose of CPA was administered, associated with either transdermal (group T) or oral (group O) 17 beta-E2. MAIN OUTCOME MEASURES: Glucose tolerance, plasma lipid level, coagulation and fibrinolysis parameters, and angiotensinogen, before and at 6 and 12 months during treatment. RESULTS: At 12 months, fasting blood glucose and basal insulin levels were significantly lower in group O than in group T. The increase in angiotensinogen was greater in group O, however, without modification in arterial blood pressure. No significant difference between the two groups was observed in lipids, coagulation, and fibrinolysis. CONCLUSION: Natural estrogens associated with CPA have no patent deleterious metabolic effect. However, the choice of oral estrogen administration seems to be better among patients with disorders such as hyperandrogenism or obesity with potential hyperinsulinism.

Administration, Cutaneous↗

PubMed1995

Accumulation of 5 alpha-reduced androgen glucosiduronates associated with impaired removal in young male hemodialysis patients.

Hypothalamic-pituitary gonadal function is commonly altered in dialysis patients. Even though an improvement in general status and well-being has been noted after recombinant human erythropoietin supplementation, no significant changes were observed in the sex hormone profile. Pituitary gonadal axis as well as 5 alpha-reduced androgen glucosiduronates (i.e. 5 alpha-androstane,3 alpha,17 beta-diol and androsterone) profiles were studied in 23 young male stable dialyzed patients and compared to an age-matched group of healthy subjects. 5 alpha-Reduced androgen glucosiduronates are products of peripheral testosterone (T) metabolism and seem to be a useful tool in assessment of the male androgen status. Their polarity facilitates their urinary excretion, and their clearance is similar to the glomerular filtration rate in healthy men. We observed 1) a pituitary-Leydig cell dysfunction supported by normal serum estradiol and T levels, low free T, and increased LH levels; 2) an alteration of the dehydroepiandrosterone (DHEA) sulfate-DHEA interconversion, reflected by a dramatic decrease in DHEA while DHEA sulfate levels remained in the normal range; 3) an accumulation of 5 alpha-reduced androgen glucosiduronates, whose removal was impaired as shown by their very low sieving coefficients (< 0.012). Taken together, the above observations are consistent with alteration of spermatogenesis with respect to dialysis duration in which earlier elevated baseline serum LH levels indicate a primary defect in Leydig cell function.

Adolescent↗

PubMed1995

Effect of oral isotretinoin treatment on skin androgen receptor levels in male acneic patients.

An oral daily dose (mean +/- SD, 0.75 +/- 0.05 mg/kg) of isotretinoin was administered for 3 months to six male patients with acne (scores of 4 and 5 according to Rosenfield). The therapy resulted in complete resolution of acne in four patients and improved acne significantly (score 1) in two patients. In accordance with recent findings, no change in serum testosterone and significant decreases in 5 alpha-dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol glucosiduronate, and androsterone glucosiduronate levels were observed after treatment. Androgen receptor status was investigated in back skin biopsies obtained in acne areas before and after 3 months of isotretinoin treatment. The treatment did not modify the binding affinity constant of skin androgen receptor (0.44 vs. 0.32 nmol/L), but it did induce a 2.6-fold decrease in its binding capacity constant (62 vs. 24 fmol/mg cytosolic protein), as assessed by Scatchard plot and confirmed immunologically by Western blot analysis. These data clearly showed that skin androgen receptor was sensitive to oral isotretinoin administration in acneic patients. The decrease in skin androgen receptor levels (this study) and the recently reported suppression of skin 5 alpha-dihydrotestosterone production by isotretinoin treatment appeared consistent with the involvement of androgen receptor and 5 alpha-dihydrotestosterone in the pathogenesis of acne. Indeed, sebum production is under androgen control, and an abnormal response of the pilosebaceous unit to androgens appears to be implicated in the pathogenesis of acne. These observations were consistent with the absence of sebum in complete androgen-insensitive patients and normal sebum production in male pseudohermaphrodites.

Acne Vulgaris↗

PubMed1995

[Value of immunoassay of hCG for the determination of high plasma concentrations].

The serum concentration of human chorionic gonadotrophin is higher in trisomy 21 than in normal pregnancy. Our study aimed at comparing 17 commercial kits, both those for measuring high concentrations and others for diagnosis and initial follow-up of pregnancy under specific conditions, ie for measuring hCG concentrations between weeks 14 and 18 of pregnancy. All kits were satisfactory; however, usual values for the gestational weeks concerned need to be established for each reagent.

Chorionic Gonadotropin↗

PubMed1995

[Functional properties of a new line of immortalized human endothelial cells].

An immortalized human endothelial cell line was obtained by transfecting umbilical vein endothelial cells in primary culture with plasmid pMK16 containing SV40 replicated origin defective gene. The essential functional properties demonstrated in these immortalized human endothelial cells also retaining the classical phenotypical characteristics of endothelial cells in primary culture are: (1) endothelin-1 secretion; (2) capacity to convert big endothelin-1 into endothelin-1; (3) the capacity to secrete IL1 beta and IL6 interleukins both spontaneously and after lipopolysaccharide (LPS) stimulation; (4) arginine transfer from the extracellular to the intracellular medium. Such stable cell line could facilitate studies of regulation of endothelin-1 production; (5) No-synthase activity; (6) binding and metabolisation of acetylated low-density lipoproteins.

Arginine↗

PubMed1994

[Late onset hyperandrogenism caused by 3-beta-hydroxysteroid dehydrogenase deficiency].

OBJECTIVES: Clinical manifestations of hyperandrogenism, including hirsutism and acne with or without dysmenorrhoea are well recognized in late onset hyperandrogenism due to deficiency in 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), yet the frequency of this deficiency in patients with post-puberty hirsutism is not well established. We therefore evaluated retrospectively this deficiency state in women who consulted our unit for manifestations suggestive of hyperandrogenism from 1990 to 1992. METHODS: We included 32 women with clinical manifestations of hyperandrogenism for whom a partial deficit in 3 beta-HSD could be searched for on the basis of hormone assays. Their mean age was 27.5 years (range 14 to 46) and the clinical manifestation was hirsutism in 21 cases, acne in 13, alopecia in 5 and dysmenorrhoea in 11. Diagnostic tests included adrenal stimulation with 0.25 mg beta 1-24 corticotrophin and immunoradioassay of plasma levels of 17-hydroxypregnenolone (17-OHPreg), 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHA) and cortisol (F). Pang's criteria for the diagnosis of partial deficiency in 3 beta-HSD were retained. We defined deficiency in 3 beta-HSD as certain when the 4 following criteria were present 60 minutes after stimulation: 17-OHPreg > 17.5 ng/ml; DHA > 20 mg/ml; 17-OHPreg/17-OHP > 9; 17-OHPreg/F.10(-3) > 53. Diagnosis was considered probable when only 3 criteria were met and was excluded in all other cases. RESULTS: Positive diagnosis of deficiency in 3 beta-hydroxysteroid dehydrogenase was made in 4 of the 32 patients and probable in 4 others. CONCLUSION: Based on our series of patients, late onset hyperandrogenism due to 3 beta-hydroxysteroid dehydrogenase deficiency would thus appear to be a relative frequent deficiency state. Since therapeutic measures can be taken, this deficiency should be carefully searched for in all young patients presenting with manifestations suggesting hyperandrogenism.

3-Hydroxysteroid Dehydrogenases↗

PubMed1994

Distinct androgen 5 alpha-reduction pathways in cultured fibroblasts and immortalized epithelial cells from normal human adult prostate.

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 50 nM.) for 2 and 4 hours, after which the testosterone metabolic profile was analyzed. Data analysis provided evidence, for the first time, of the existence of two different 5 alpha-reduced metabolic pathways. Stromal cells preferred the androsterone pathway via the oxidative androstenedione formation, whereas epithelial cells preferred the reductive 5 alpha-dihydrotestosterone pathway. These two 5 alpha-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-5-alpha-reductase drugs to the management of benign prostate hyperplasia.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed1994

The application of a new highly-sensitive radioimmunoassay for plasma 21-deoxycortisol to the detection of steroid-21-hydroxylase deficiency.

21-deoxycortisol (21-DF) is a steroid of strictly adrenal origin formed by the 11-hydroxylation of 17-hydroxyprogesterone. This metabolic pathway is minor in normal subjects, in whom basal plasma concentrations range from 0.03 to 0.63 nmol/L and from 0.865 to 1.50 nmol/L after adrenocorticotrophic hormone (ACTH; Synacthène Immédiat, Ciba/Geigy, France). However, this metabolic pathway becomes major in 21-hydroxylase-deficient patients: in those who have the classical form of congenital adrenal hyperplasia (CAH) basal plasma 21-DF levels can attain more than 144 nmol/L. The synthesis of two isomers, E and Z, of the 21-deoxycortisol-3-carboxymethyloxime (CMO) hapten enabled us to prepare the corresponding E and Z immunogens by coupling them to bovine serum albumin (BSA), as well as the corresponding iodinated E and Z 21-DF-3-CMO-histamine tracers. We developed a very sensitive radioimmunoassay for 21-DF in plasma by associating an anti-21-DF-3-CMO-BSA-E isomer antibody to an iodinated 21-DF histamine-Z isomer (standard curve IC 50 = 8 pg/tube). This plasma 21-DF radioimmunoassay allowed diagnosis of the classical form of CAH in untreated newborn (basal 21-DF levels greater than 144 nmol/L), as well as the late-onset form (post-ACTH 21-DF levels greater than 11.54 nmol/L), and also permitted detection of 21-hydroxylase-deficient heterozygotes of both forms of CAH among the general population (post-ACTH 21-DF levels between 2.02 and 9.52 nmol/L).

Adolescent↗

PubMed1994

Evidence for decreased androgen 5 alpha-reduction in skin and liver of men with severe acne after 13-cis-retinoic acid treatment.

To investigate the effect of 13-cis-retinoic acid (13-cis-RA) treatment on androgen metabolism in men with severe nodulocystic acne, eight men with severe acne received an oral daily dose of 0.7 mg/kg 13-cis-RA over 3 months. Exploration of androgen metabolism in serum samples, 24-h urine collections, and skin biopsies obtained before and at the end of the treatment revealed no significant alterations in serum levels of either adrenal or gonadal androgens. However, the treatment did induce significant decreases in serum levels of the 5 alpha-reduced androgens: 5 alpha-dihydrotestosterone (P < 0.02), androsterone glucosiduronate (P < 0.04), and 5 alpha-androstan-3 alpha, 17 beta-diol glucosiduronate (P < 0.004). Unlike serum, the urinary 5 alpha-reduced metabolites 5 alpha-androstan-3 alpha, 17 beta-diol and androsterone did not vary significantly despite a decrease in the excretion of the latter. Moreover, a marginally significant increase in urinary excretion of etiocholanolone, very similar to the decrease in androsterone excretion, was observed. The ratio of androsterone to etiocholanolone decreased significantly (P < 0.004) after 13-cis-RA therapy and suggested a metabolic deviation from the androgen 5 alpha- to 5 beta-reduction pathway in the liver. The most pronounced effect was observed in skin biopsies, which lost 80% of their ability to form 5 alpha-dihydrotestosterone (P < 0.001). It is concluded that 13-cis-RA therapy in men with severe nodulocystic acne did not alter gonadal or adrenal functions, but it did induce 1) a highly significant decrease in 5 alpha-dihydrotestosterone formation by skin biopsies; 2) significant decreases in serum 5 alpha-dihydrotestosterone, androsterone glucosiduronate, and 5 alpha-androstan-3 alpha, 17 beta-diol glucosiduronate; and, finally, 3) deviation of the liver androgen 5 alpha- to 5 beta-reduction pathway. The effect of 13-cis-RA treatment on severe acne is consistent with the dramatic decrease in androgen 5 alpha-reduction observed mainly in the skin.

Acne Vulgaris↗

PubMed1994

Hirsutism and acne in women: coordinated radioimmunoassays for eight relevant plasma steroids.

We developed and validated a coordinated set of RIAs for the following eight steroids in single small aliquots (< or = 1 mL) of plasma: androstenedione, dehydroepiandrosterone, 11-deoxycortisol, 21-deoxycortisol (21-DF), 11 beta-hydroxyandrostenedione, 17 alpha-hydroxypregnenolone (17-Hpreg), 17 alpha-hydroxyprogesterone, and testosterone. Samples were extracted and then chromatographed on celite microcolumns. Radioiodinated tracers were used for two of the assays (17-Hpreg and 21-DF). Tritiated tracers and scintillation proximity assay counting were used to give separation-free procedures for the other six assays, which considerably improved their practicability and reproducibility. The basal and postadrenocorticotropic hormone plasma values for these steroids in normal women sampled in the follicular phase are presented. Finally, the measurement of the eight steroids as a diagnostic method is evaluated with reference to data from 203 patients with hirsutism and (or) acne.

17-alpha-Hydroxypregnenolone↗