Androgen binding capacity and 5 alpha-reductase activity in pubic skin fibroblasts from hirsute patients.
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.
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000728:Androgens / Q000378:metabolism*; D000734:Androstenediols / Q000097:blood; D005260:Female; D006628:Hirsutism / Q000378:metabolism*; D006801:Humans; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism*; D011485:Protein Binding; D011944:Receptors, Androgen / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D012737:Sex Factors; D012867:Skin / Q000201:enzymology*; D013739:Testosterone / Q000097:blood
D000728:Androgens; D000734:Androstenediols; D011944:Receptors, Androgen; D011987:Receptors, Steroid; D013739:Testosterone; D010088:Oxidoreductases; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase