3.睾丸性androgensの生成と変換:附:ヒト副腎におけるandrogensの生成

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Cellular elements of testicular tissue consist of three major components, namely spermatogenic cells, Sertoli cells and interstitial cells. Any definite evidences that spermatogenic cells produce androgens have not yet been obtained. Electron-microscopic studies in our laboratory revealed that interstitial cells were rich in mitochondria and endoplasmic reticulum which are indispensable for steroid hormone production, in contrast to poor development of those in Sertoli cells. Also, the activity of 38-hydroxysteroid dehydrogenase, which biotransforms Δ5-3β-hydroxysteroids to Δ4-3-ketosteroids is demonstrated to be localized only in interstitial cells of fetal as well as mature testes. From these facts and other many experimental findings in literature, it is reasonably concluded that testicular androgens are produced in the interstitial cell. Enzymes related to biosynthesis of teststerone from pregnenolone are 3β-hydroxysteroid dehydrogenase (3β-DHG), 17α-hydroxylase (17α-OHase), 17α-hydroxypregnene C17-C20 lyase (C17-C20 lyase) and 17β-hydroxysteroid dehydrogenase (17β-DHG). These enzymes are demonstrated to be localized in microsomal fraction, when the homogenate of testicular tissue is divided into subcellular fractions by conventional differential centrifugation, and require NADPH as cofactor except 3β-DHG, which requires NAD+as hydrogen receptor. When testicular microsomes of aged men (five cases) were incubated with pregnenolone-4-14C, no metabolites other than Δ4-3-ketosteroids were obtained, while 3β-DHG showed low activity and others above described were highly active (particulars will be published elswhere). From these results, in vitro biosynthetic pathway of of androgens in human testes is considered as follows ; pregnenolone→progesterone→17α-hydroxyprogesterone→.Δ4-androstenedione→testosterone. This metabolic pathway is also ascertained in the same experiment with homogenates of mature rat testes. There are some other enzymes related to androgen bioconversion in testes. 1) 20α-Hydroxysteroid dehydrogenase in human testes converts progesterone to 20α-hydroxypregn-4-en-3-one and 17α-hydroxyprogesterone to 17α-, 20α-dihydroxypregn-4-en-3-one, which inhibits the activity of C17-C20 lyase and furthermore, is unsuitable for C17-C20 lyase. 2) 16α-Hydroxylase shows substrate specificity for progesterone, but the meaning in testes remains unexplained. 3) Δ4-5α-reductase and 3α-hydroxysteroid dehydrogenase are highly active in testes of immature and hexestrol-treated rats. As a result of high activities of these enzymes, 5α-saturated and 3α-hydroxylated steroids are mainly produced in these testes in vitro. When male animals were treated with androgens or estrogens, androgen productionin testes is lowered by feed-back mechanism. By incubation studies of animal and human testicular tissue with appropriate precursor steroids, it was found that 17α-OHase, C17-C20 lyase, 17β-DHG and 16a-OHase were significantly inhibited by the treatment, whereas 3β-DHG was not affected. Human testes were affected by hexestrol administration as above stated. But, in rat testes treated with large doses of hexestrol, peculier changes of steroidal metabolic pathway were observed : Enzyme activities related to androgen biosynthesis were inhibited and Δ4-5α-reductase and 3α-hydroxysteroid dehydrogenase were significantly activated. The results suggest the direct effect of exogenous synthetic estrogen upon testes. Androgen biosynthesis in vitro was proved, in human adrenals. 17α-OHase in human adrenals is highly active,
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3.睾丸性androgensの生成と変換:附:ヒト副腎におけるandrogensの生成

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