Androgen Metabolism

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The causes of hyperandrogenism are multiple (Table 12.1). Skin androgenization in women may be due to abnormal production of andro-gens by the ovaries and/or the adrenal glands, and/or to an excessive response of target cells in the pilosebaceous unit (peripheral androgen-ism) [6].

Androgens [testosterone and the less potent androgens in women A4-androstenedione (A4A) and dehydroepiandrosterone (DHEA)] are synthesized by the adrenals (mostly DHEA and its sulfate - SDHEA) and the ovaries (mostly A4A) and may be subsequently transformed into oestrogens through the aromatization of the molecules. Sex hormone binding globulin (SHBG) synthesized in the liver is the major carrier protein for androgens and oestradiol. Only free androgens, unbound to SHBG, are directly active on target cells. In tissues, androgens are first metabolically transformed into the active form dihydrotestosterone (DHT), which then binds to androgen receptors (AR) [16].

Table 12.1. Causes of hyperandrogenism

1. Polycystic ovary syndrome (PCOS)

2. Non-classic adrenal hyperplasia with 21-hydroxylase deficiency

3. Skin hypersensitivity = peripheral hyperandrogenism:

- with hirsutism (idiopathic)

- and/or acne or androgenic alopecia

4. Drugs

- androgenic progestins

- OP contraception with androgenic progestins

- adrenal and ovarian tumours

- Cushing's syndrome

Sebaceous glands, but also keratinocytes from the acroinfundibulum and dermal papilla cells, can synthesize androgens de novo from cholesterol or by locally converting weaker androgens (A4A and DHEA) to testosterone and DHT. As in other classic steroidogenic organs, the pilosebaceous unit expresses the major enzymes involved in androgen metabolism, namely steroid sulfatase, 3|3-, 3a- and 17|3-hydroxys-teroid dehydrogenases, and 5a-reductase, which converts testosterone into DHT. Furthermore aromatase, which converts testosterone into oestradiol, is localized to sebaceous glands and to both outer and inner root sheath cells of anagen terminal hair follicles. This hormone may play a "detoxifying" role by removing excess androgens [5].

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