Intracrinology and the skin.
The skin, the largest organ in the human body, is composed of a series of androgen-sensitive components that all express the steroidogenic enzymes required to transform dehydroepiandrosterone (DHEA) into dihydrotestosterone (DHT). In fact, in post-menopausal women, all sex steroids made in the skin are from adrenal steroid precursors, especially DHEA. Secretion of this precursor steroid by the adrenals decreases progressively from the age of 30 years to less than 50% of its maximal value at the age of 60 years. DHEA applied topically or by the oral route stimulates sebaceous gland activity, the changes observed being completely blocked in the rat by a pure antiandrogen while a pure antiestrogen has no significant effect, thus indicating a predominant or almost exclusive androgenic effect. In human skin, the enzyme that transforms DHEA into androstenedione is type 1 3beta-hydroxysteroid dehydrogenase (type 1 3beta-HSD) as revealed by RNase protection and immunocytochemistry. The conversion of androstenedione into testosterone is then catalyzed in the human skin by type 5 17beta-HSD. All the epidermal cells and cells of the sebaceous glands are labelled by type 5 17beta-HSD. This enzyme is also present at a high level in the hair follicles. Type 1 is the 5alpha-reductase isoform responsible in human skin for the conversion of testosterone into DHT. In the vagina, on the other hand, DHEA exerts mainly an estrogenic effect, this effect having been demonstrated in the rat as well as in post-menopausal women. On the other hand, in experimental animals as well as in post-menopausal women, DHEA, at physiological doses, does not affect the endometrial epithelium, thus indicating the absence of DHEA-converting enzymes in this tissue, and avoiding the need for progestins when DHEA is used as hormone replacement therapy.
Labrie
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Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL), Québec City, Canada. fernand.labrie@crchul.ulaval.ca
Luu-The
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Labrie
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Pelletier
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El-Alfy
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D000728:Androgens / Q000494:pharmacology; D000818:Animals; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D004704:Endocrinology / Q000379:methods*; D004717:Endometrium / Q000187:drug effects; D004798:Enzymes / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006801:Humans; D012867:Skin / Q000187:drug effects; D012879:Skin Physiological Phenomena; D013256:Steroids / Q000096:biosynthesis; D014621:Vagina / Q000187:drug effects
D000728:Androgens; D004798:Enzymes; D004967:Estrogens; D013256:Steroids; D003687:Dehydroepiandrosterone