Acne may be mediated by serum androgens, locally produced androgens, or a combination of both. Insights have been gained regarding the local metabolism of androgens within sebaceous glands (9). Such insights may be of benefit in the design of new acne therapies. The skin and sebaceous gland are capable of producing and metabolizing androgens (9). DHEAS is the major adrenal androgen precursor. It circulates in the blood stream in relatively high levels compared with other hormones with the exception of cortisol. In fact, in for review, see Ref. postmenopausal 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 age 30 to less than 50% of its maximal value at age 60 (10). The enzyme 3^-hydroxysteroid dehydrogenase (3^-HSD) acts on DHEA to convert it to androstenedione (Fig. 1). This conversion may take place in the adrenal gland and tissues such as the sebaceous gland, where activity of the 3^-HSD enzyme has been identified by several investigators (11-13). The reversible conversion of androstenedione into testosterone is then catalyzed in the human skin by 17^-HSD, a member of the short chain alcohol dehydrogenases that are related to retinol metabolizing enzymes (14-18). This is a reversible enzyme that can oxidize and reduce both androgens and estrogens. It is responsible for converting the weak androgen androstenedione into the more potent androgen testosterone. It can also interconvert weak and potent estrogens such as estrone and estradiol. The 17^-HSD enzyme may represent a regulatory point in androgen and estrogen metabolism within the skin.
DHT is produced from testosterone within peripheral tissues such as the skin by the action of the 5a -reductase enzyme. Two isozymes of 5a -reductase have been identified (19). The type 1 isozyme is active within the sebaceous gland (20,21). The type 2 isozyme is most active in the prostate gland, where it can be inhibited by drugs such as finasteride. Activity of 5a-reductase and 17^-HSD exhibits regional differences depending upon the source of the sebaceous glands (9). In skin that is prone to acne, such as facial skin, activity of the type 1 5a-reductase in sebaceous glands is greater than in sebaceous glands obtained from nonacne-prone skin (20). This implies that more DHT is being produced in sebaceous glands from facial skin compared with other areas of the body that are not prone to develop acne. The net effect of the activity of these two enzymes is the greater production of potent androgens such as testosterone and DHT within sebaceous glands of facial areas, which may in part account for the development of acne in these areas.
17, 20 lyase
17, 20 lyase
FIGURE 1 The steroidogenic pathway. Abbreviations: HSD, hydroxysteroid dehydrogenase; P450scc, P450 side chain cleavage enzyme; StAR, steroidogenic acute regulatory protein.
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