Sertoli Cell Capacity to Metabolize Progesterone: Variation with Age and the Effect of Follicle-Stimulating Hormone*

Abstract

Sertoli cells were isolated from rats with Sertoli cell-enriched testes at 6–65 days of age, and their in vitro capacity to convert ¹⁴C- or³H-labeled progesterone to 20α-hydroxy- 4-pregnen-3-one (20α-DHP), 3α-hydroxy-5α-pregnan-20- one (3α-HP), 3α,20α-dihydroxy-5α-pregnane (DIOL), 5α-pregnane- 3,20-dione, 17α-hydroxy-4-pregnen-3,20-dione (17α-HP), testosterone (T), and androstenedione was examined at different ages and under the influence of tropic hormones. The identity of the metabolites was established by the employment of thin layer chromatography, gas chromatography, derivatization, and crystallization methods, and quantitation involved calculation of the recovery of a second tracer or standards. Autoradiography of thin layer chromatography-separated [^l4C]progesterone metabolites showed marked differences between Sertoli cells from 10-and 65-day-old rats. Quantitation of products at different ages revealed that the conversion of progesterone to 20α-DHP, 3α- HP, and DIOL was highest in Sertoli cells from 10-day-old rats (3075,655, and 468 ng/mg protein· 20 h, respectively); conversion to these steroids was significantly less in cells from 6-, 25-, 32-, and 65-day-old rats. In contrast, conversion to 17α-HP and T was highest in cells from 6-day-old rats (120 and 68 ng/mg-20 h, respectively) and then declined rapidly by 10 days, reaching minimum values by 25 days, and increased gradually to 65 days. Production of androstenedione was 12–23 ng/mg-20 h from 6–25 days and then increased to 280 ng/mg · 20 h by 65 days. FSH resulted in significant increases in progesterone conversion to 5a-pregnane-3,20-dione, DIOL, and 3α-HP in Sertoli cells from 6-, 10-, and 17-day-old rats, but not in cells from older animals. The conversions of progesterone to 20α-DHP and 17α- HP were not influenced by FSH at any of the ages studied; the production of T was slightly increased by FSH at 10 and 17 days. LH and TSH did not elicit any increases in steroid synthesis; however, LH treatment resulted in a significant decrease in 20α- DHP. The results indicate that coincident with the onset of spermatogenesis, Sertoli cells exhibit increased C-21 5α-reductase, 3α-hydroxysteroid oxidoreductase (3α-HSO), and 20α-HSO activities; the 5a-reductase and 3a-HSO activities are further stimulated by FSH at this time, but not in older rats. While the production by Sertoli cells of 5α-reduced C-21 steroids increases markedly between 6–10 days, conversions to 17α-HP and T are significantly educed. On the other hand, 17α-hydroxylase and 20α-HSO are not stimulated by tropic hormones at any age. (Endocrinology108: 597, 1981)