Androgen Biosynthesis in Developing Ovarian Follicles Evidence that Luteinizing Hormone Regulates Thecal 17α-Hydroxylase and C17–2o-Lyase Activities*

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Abstract
In the pregnant rat, small antral follicles require increased LH activity to promote estradiol synthesis and preovulatory follicular development. To determine which steps in the biosynthesis of estradiol require increased LH activity, we compared the abilities of small antral follicles (from rats on day 16 of pregnancy) and preovulatory follicles (from rats on day 23 of pregnancy) to 1) produce progesterone, androgen, and estradiol (measured by RIA), and 2) metabolize [3H]progesterone or [3H]17α-hydroxyprogesterone to successive steroids in the Δ4- pathway. Although small antral follicles produce 6 ng progesterone during a 4-h incubation with hCG, 8-bromo-cAMP, or human FSH, less than 50 pg testosterone or estradiol were detected by RIA in the same incubates. Small antral follicles incubated in the presence of [3H]progestins produced little authentic tritiated 5α-pregnan-3,20-dione, 3β-hydroxy-5α-pregnane-20-one, pregnan-20-one, 17α-hydroxyprogesterone, androstenedione, testosterone, or estradiol. In contrast, preovulatory follicles produced (as determined by RIA) approximately 80 ng progesterone, 5 ng androgen, and 10 ng estradiol in response to hormone or 8-bromo-cAMP and metabolized large amounts of the [3H]progestins to estradiol. Accumulation of authentic [3H]testosterone, however, did not increase in response to 8-bromo-cAMP and was much less than the androgen detected by RIA. Because incubation of individual compartments from preovulatory follicles failed to produce the large quantities of androgen obtained with intact follicles, and because human FSH as well as hCG and 8-bromo-cAMP stimulated the accumulation of this material by intact follicles, granulosa cells may play an important role in the synthesis of this material. The results of this study demonstrate that small antral follicles produce progesterone in response to gonadotropins and cAMP, but fail to convert it to estradiol. The inability of these follicles to metabolize [3H]progestines to other Δ4steroids suggests that thecal 17α-hydroxylase and C17–20-lyase activities limit testosterone production at this stage of follicular development. We propose, therefore, that small increases in serum LH activity regulate the activity of these enzymes, thereby permitting increased androgen and estradiol production and promoting preovulatory follicular development.

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