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Cellular sites and gonadotropic control of human follicular estrogen secretion have been assessed by culturing the theca and granulosa components separately under different hormonal conditions. Granulosa cells from human follicles were grown in chemically defined media containing gonadotropins and/or testosterone (T) for 24 h. The production of 17 beta-estradiol (E2) by cells cultivated in T-free media with or without FSH was very low during the culture period. There was a highly significant increase (P less than 0.001) in E2 production when T alone was added and a more marked increase was consistently noted in the presence of FSH and T. In all cases, hCG failed to exert any significant effect on E2 production by granulosa cells in the presence or absence of T. No treatments examined altered the E2 production of thecal cells during a 24-h culture period and the amounts of E2 released into media were negligible when compared with levels produced by granulosa cells from the same follicles. It is concluded that granulosa cells but not thecal cells are the prime site of follicular estrogen production and that FSH regulates estrogen secretion by nonluteinized granulosa cells of the human follicle.

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