Gene expression of type 2 17 beta hydroxysteroid dehydrogenase in scalp hairs of hirsute women.

Androgens are the main hormonal regulators of human hair growth and they are related to clinical conditions such as hirsutism. The aim of this study was to analyze the gene expression of androgen receptor (AR) and type 2 17 beta hydroxysteroid dehydrogenase (17 beta-HSD) in keratinocytes of plucked scalp hairs from hirsute patients and normal subjects. We studied 58 women with hirsutism (31 with polycystic ovary syndrome (PCOS), 27 with idiopathic hirsutism (IH)); 15 control women; and 10 control men. Hirsutism was assessed by a modified Ferriman-Gallwey method. Hormonal status was assessed between days 2 and 10 of the menstrual cycle or on any day when the patients were amenorrheic. AR and type 2 17 beta-HSD mRNA levels were estimated by reverse transcription-polymerase chain reaction (RT-PCR). AR expression was similar in all groups. Type 2 17 beta-HSD gene expression in untreated hirsute patients was lower (2.1+/-0.10) than in normal women (3.1+/-0.17), and similar to men (1.8+/-0.22). Comparing hirsute patients, type 2 17 beta-HSD expression was higher in treated PCOS (3.0+/-0.34 versus 2.2+/-0.13) and IH patients (2.5+/-0.19 versus 2.0+/-0.15); hirsutism score was lower (P=0.003, PCOS; P=0.003, IH); and SHBG levels were higher (P=0.001, PCOS; P=0.024, IH) in treated patients. The free androgen index was lower in treated women (P=0.024 for the IH group). In conclusion, the lower expression of type 2 17 beta-HSD mRNA in scalp hairs of untreated hirsute patients suggests androgen metabolism disturbances with predominance of more potent androgens, as occurs in men. The enzyme's higher gene expression in treated hirsute patients could be an indirect evidence of restored enzyme activity and intracellular androgen metabolism.

The 5alpha-reductase type 1, but not type 2, gene is expressed in anagen hairs plucked from the vertex area of the scalp of hirsute women and normal individuals.

The aim of the present study was to determine the expression of the genes for type 1 (SDR5A1) and type 2 (SDR5A2) 5alpha-reductase isoenzymes in scalp hairs plucked from 33 hirsute patients (20 with polycystic ovary syndrome and 13 with idiopathic hirsutism) and compare it with that of 10 men and 15 normal women. SDR5A1 and SDR5A2 expression was estimated by RT-PCR using the gene of the ubiquitously expressed protein 2-microglobulin as an internal control. The results are expressed as arbitrary units in relation to beta2-microglobulin absorbance (mean SEM). SDR5A2 expression was not detected in any hair samples analyzed in this study. No differences were found in SDR5A1 mRNA levels between men and normal women (0.78+/-0.05 vs 0.74+/-0.06, respectively). SDR5A1 gene expression in the cells of hair plucked from the scalp of normal women (0.85+/-0.04) and of women with polycystic ovary syndrome (0.78+/-0.05) and idiopathic hirsutism (0.80+/-0.06) was also similar. These results indicate that SDR5A1 gene expression in the follicular keratinocytes from the vertex area of the scalp seems not to be related to the differences in hair growth observed between normal men and women and hirsute patients. Further studies are needed to investigate the expression of the 5alpha-reductase genes in other scalp follicular compartments such as dermal papillae, and also in hair follicles from other body sites, in order to elucidate the mechanism of androgen action on the hair growth process and related diseases.

Prevalence of 21-hydroxylase-deficient nonclassic adrenal hyperplasia and insulin resistance among hirsute women from Puerto Rico.

OBJECTIVE: To determine the prevalence of 21-hydroxylase (21-OH)-deficient nonclassic adrenal hyperplasia (NCAH) and insulin resistance in hirsute women from Puerto Rico. DESIGN: Cross-sectional prospective study. SETTING: Clinical research center. PATIENT(S): 100 consecutive untreated hirsute women. MAIN OUTCOME MEASURE(S): Fasting total T, free T, DHEAS, insulin, and glucose were measured, and a 60-minute acute ACTH-(1-24) stimulation for 17-hydroxyprogesterone (17-HP) was performed. A diagnosis of 21-OH-deficient NCAH was considered when the stimulated 17-HP level was >30.3 nmol/L. The glucose/insulin ratio was calculated as a measure of insulin resistance (normal value, > or =4.5). RESULT(S): Patients had a mean (+/-SD) age of 26.8+/-6.6 years; 82 were oligomenorrheic. Overall, 12%, 8%, and 60% of patients had elevated levels of DHEAS, total T, or free T, respectively. One patient was identified as having 21-OH-deficient NCAH. Eight women, none of whom had NCAH, were found to be hyperglycemic; four of these women had type 2 diabetes mellitus. Excluding hyperglycemic patients, a glucose/insulin ratio of <4.5, consistent with IR, was found in 51.7%. CONCLUSION(S): The prevalence of 21-OH-deficient NCAH among patients from Puerto Rico does not differ significantly from that reported for other non-Jewish, non-Hispanic white populations.

Aspectos genéticos e dúvidas diagnósticas da deficiência da 3 beta-hidroxiesteróide desidrogenase: atualizaçäo / Genetic and diagnostic aspects on 3 beta-hidroxisteroid dehidrogenase defficiency: an update

Nos últimos 10 anos, muito tem-se publicado sobre a diminuiçao da atividade da 3 beta-hidroxiesteróide desidrogenase (3 beta-HSD) por ocasiao da infância, menarca ou mesmo após, determinando por um lado hiperplasia supra-renal congênita e na área ginecológica síndrome dos ovários policísticos devido a instalaçao de um meio androgênico coadjuvante do desvio da funçao ovulatória. Tida como a deficiência enzimática mais freqüente na forma de início tardio das hiperplasias supra-renais, seu diagnóstico era feito através apenas de estudos hormonais em que se comparavam os precursores delta 5 aos delta 4 da esteroidogênese. Tais dados, aceitos como universais, começaram a ser questionados a partir das descobertas recentes da localizaçao dos genes que codificam a atividade enzimática da 3 beta-HSD. Esta revisao procura mostrar os avanços na conduçao diagnóstica desta patologia a partir das últimas publicaçoes sobre o tema. Questiona-se por fim a existência da forma tardia desta enzimopatia.

[3 beta-hydroxysteroid dehydrogenase defect: frequency of presentation in a sample of Chilean hirsute women]. / Defecto de 3 beta hidroxiesteroide deshidrogenasa: frecuencia de presentación en una muestra de mujeres chilenas hirsutas.

The defect of 3 beta hydroxysteroid dehydrogenase (3 beta HSD) is frequent among hirsute women and clearly dependent on the ethnic composition of the studied population. Our aim was to study the frequency of 3 beta HSD deficit in a group of Chilean hirsute women. Basal and post ACTH concentrations of cortisol, 17 hydroxyprogesterone and 17 hydroxypregnenolone were measured by RIA in 40 hirsute post puberal women and in 15 normal age matched female volunteers. Criteria for considering a 3 beta HDS deficit were 17 hydroxypregnenolone values and 17 hydroxypregnenolone/17 hydroxyprogesterone and 17 hydroxypregnenolone/cortisol ratios after ACTH stimulation over the 95% confidence intervals of normal women. Basal dehydroepiandrosterone sulphate and testosterone levels were also measured in hirsute women. All samples were obtained during the follicular phase of the menstrual cycle. ACTH stimulated hormone values and ratios were diagnostic for 3 beta HDS deficit in 7.5% of hirsute women. Basal testosterone was over 80 ng/dl in 47.5% and dehydroepiandrosterone sulphate over 3.9 micrograms/ml in 52.5% of these women. There was no correlation between dehydroepiandrosterone or testosterone values and ACTH stimulated hormone values. It is concluded that 3 beta HSD is frequent in hirsute women and that its diagnosis requires the determination of ACTH stimulated 17 hydroxypregnenolone values and 17 hydroxypregnenolone/17 hydroxyprogesterone ratio.