Androgen Binding Capacity and 5α-Reductase Activity in Pubic Skin Fibroblasts from Hirsute Patients*

Abstract

We have measured the total (cytosolic plus nuclear) androgen binding capacity of pubic skin fibroblasts from nine patients with hirsutism of various origin. Confluent intact cell monolayers were incubated with increasing concentrations (0.05-2 nM) of [3H]dihydrotestosterone ([3H]DHT) with or without a 200-fold excess of unlabeled DHT. The androgen binding capacities (mean +/- SD) were similar in normal men (411 +/- 171 fmol/mg DNA), women (310 +/- 103 fmol/mg DNA), and hirsute patients (313 +/- 141 fmol/mg DNA) regardless of the plasma androgen levels. In contrast, the 5 alpha-reductase level in pubic skin fibroblasts (mean +/- SD) was, as previously described, higher in hirsute women (3.3 +/- 2.6 fmol/micrograms DNA . h) than in normal women (1.1 +/- 0.6 fmol/microgram DNA . h; P less than 0.05). We conclude from these data that: 1) increased androgen binding capacity cannot be held responsible for hypersensitivity to androgens in hirsutism; 2) the androgen receptor is not regulated by androgens in human skin, as similar levels are observed in men, women, and hirsute patients; 3) this contrasts with 5 alpha-reductase activity and emphasizes the importance of this enzyme as an amplifier of androgen action in areas where it is stimulated by androgens, such as pubic skin.

A Case-controlled Comparative Hospital-based Study on the Clinical, Biochemical, Hormonal, and Gynecological Parameters in Polycystic Ovary Syndrome

“…The predominant being 5α-R type 1 (SDR5A1) is found majorly in skin [28] . A rise in 5a-reductase activity was seen in genital and pubic skin fibroblasts from hirsute patients compared to the skin of normal women [29,30] .…”

Puberty in Subjects with Complete Androgen Insensitivity Syndrome

“…The amino acid residue 866 lies within the AR steroid-binding domain [8] and the Ins866 in patient 9 makes the formation of a functional AR-steroid complex impossible. In patients 4, 5 and 8, who were older and were unavailable at the time DNA analysis, an AR-binding assay was performed, confirming complete androgen resistance [9]. Non-parametrical tests were used for statistical analysis: the Wilcoxon signed rank sum test for the comparison of the age at peak height velocity of CAIS patients versus that of normal French boys and girls, and the Wilcoxon matched paired signed rank sum test for the comparison of the adult heights of CAIS patients versus their male and female target heights (p < 0.05).…”

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

“…More recently, an increased androgen binding capacity was observed in scalp hair cells of balding men (7). However, no consistent difference has been found thus far in the number or function of the androgen receptor in hirsute patients compared to normal subjects (8,9).…”

“…The 5α-reductase isoenzyme predominant in the skin is type 1 (SDR5A1) (15), which has 60% homology with 5α-reductase type 2 (SDR5A2) that is characteristic of the prostate gland (14). An increase in 5α-reductase activity was demonstrated in genital and pubic skin fibroblasts from hirsute patients in comparison to the skin of normal women (8,16). These studies have reported an increase in 5α-reductase activity even in IH, which is characterized by the absence of elevated plasma androgen levels (17).…”