TESTOSTERONE 5α-Reduction IN THE SKIN OF NORMAL SUBJECTS AND OF PATIENTS WITH ABNORMAL SEX DEVELOPMENT

Abstract

Human pubic skin was obtained from normal subjects and patients with abnormal sex differentiation. Skin samples (200 mg) supplemented with NADPH, were incubated for 1 h with labelled testosterone. The conversion of testosterone to dihydrotestosterone1), 3\g=a\-and 3\g=b\-androstanediol was calculated. This conversion averaged 14.9 \m=+-\ 3.4 % (se) in 11 normal men and 3.6 \ m=+-\1.4 % (se) in 8 normal women. In 4 children as in 4 young hypogonadotrophic hypogonadal men, the conversion rate of testosterone to 5\g=a\-reducedmetabolites was low (0.8 to 3.5%) and increased at puberty (13.5 to 19.2%). After administration of HCG for 3 months to 1 of the hypogonadal men, it reached 30.2 %. Inversely, the formation of dihydrotestosterone and androstanediols from testosterone was suppressed in 2 men treated with large doses of oestrogen. In 3 subjects with an incomplete form of testicular feminization syndrome, the conversion rate of testosterone to 5\g=a\-reducedmetabolites was in the normal male range (6.4 to 18.3%), whereas it was low in one case of the complete form of the syndrome (1.5%). In 9 women with idiopathic hirsutism the rate of 5\g=a\-reducedmetabolites recovered from testosterone was close to that of normal men (13.5 \ m=+-\5.5% (se). From theseresults, it is postulated that in human subjects, there is a good correlation between hair growth in skin from a sexual area and the extent of testosterone 5\g=a\-reductionin this tissue. Such an enzymatic activity 0 The following trivial names have been used: Dihydrotestosterone = 17/?-hydroxy-5aandrostan-3-one; androstenedione = 4-androstene-3,17-dione; 3ci-androstanediol = 5aandrostane-3«,17/?-diol; 3/î-androstanediol = 5«-androstane-3/5\17/?-diol; androstanediols = 3a-androstanediol + 3/i-androstanediol.

Cultured human skin fibroblasts: a model for the study of androgen action

“…Recent studies with cultured human skin fibroblasts have suggested that 5c~-reductase activity may be androgen-dependent (23), similar to that reported for pubic skin homogenates by the same investigators (24,25). Enzyme activity from male foreskin fibroblasts was higher than from female pubic skin fibroblasts, with intermediate levels observed for pubic skin fibroblasts from hirsute women (23).…”

Hormonal Evaluation of a Large Kindred with Complete Androgen Insensitivity: Evidence for Secondary 5α-Reductase Deficiency*

“…the pubic area) and barely detectable in pubic skin homogenates of patients with complete androgen insensitivity, hypogonadal males, and prepubertal children. In children, a pubertal increase in 5a-reductase activity in pubic skin was noted, concomitant with a pubertal increase in circulating androgens (34,51). In contrast, in genital (labial) skin homogenates of adult subjects with complete androgen insensitivity, normal 5a-reductase activity was found.…”

Decreased Urinary C19and C21Steroid 5α-Metabolites in Parents of Male Pseudohermaphrodites with 5α- Reductase Deficiency: Detection of Carriers*

“…These data imply that in TF subjects, the decreased 5a-reductase(s) activity is mainly peripheral rather than splanchnic in origin. It has been demonstrated that 5a-reductase activity is barely detectable in pubic skin of patients with TF (14). It has also been shown that in normal fibroblasts cultured from pubic skin, DHT binding to the cytosol receptor can increase 5a-reductase activity.…”