Mechanism of action of androgen in hair follicles.
In order to investigate the mode of action of testosterone (T) on human hair follicles we studied the metabolism of T and localization of androgen receptors in outer root sheath cells (ORSC) and dermal papilla cells (DPC) from different body sites. T was principally metabolized to androstenedione (delta 4) even in beard ORSC as well as epidermal keratinocytes (EK), and the ratio of apparent 5 alpha-reductase (5 alpha-R) to 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) did not differ between these two kinds of cells. The 5 alpha-R activity in beard DPC was 3 times as high as that in occipital scalp and axillary DPC. The 5 alpha-R of beard DPC exhibited a narrow optimum pH of 5.5, which is characteristic of type 2 enzyme present in androgen target cells. In contrast, 5 alpha-R of DPC from axillary and occipital scalp hair showed a broad optimum pH range between 6.5-9.0 corresponding to type 1 5 alpha-R. Androgen receptors were detected in the DPC of beard and axillary hair follicles, but not in those of occipital scalp hair follicles using immunohistochemical staining with polyclonal anti-androgen receptor antibody. Epithelial cells of the hair bulb were not stained by the antibody. Androgen receptors were also detected in the nuclei of cultured beard and axillary DPC, but the DPC from occipital scalp hair follicles showed little staining with the antibody. We also examined the effects of T on the DNA synthesis and proliferation of cultured ORSC and DPC. T did not have a proliferative effect on either type of cell when cultured alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Itami
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Department of Dermatology, Oita Medical University, Japan.
Sonoda
T
T
Kurata
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Takayasu
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S
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000735:Androstenedione / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D042944:Cholestenone 5 alpha-Reductase; D017373:Cyproterone Acetate / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D006197:Hair / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism / Q000494:pharmacology*
D011944:Receptors, Androgen; D013739:Testosterone; D000735:Androstenedione; D017373:Cyproterone Acetate; D004247:DNA; D010088:Oxidoreductases; D015067:17-Hydroxysteroid Dehydrogenases; D042944:Cholestenone 5 alpha-Reductase