Ovary

Interactions Between Androgen and Growth Factors in Granulosa Cell Subtypes of Porcine Antral Follicles

Abstract
Androgens acting via the androgen receptor (AR) have been implicated in regulation of folliculogenesis in many animal species. These effects are possibly mediated via enhancement of FSH and/or IGF-1 activity in granulosa cells, which contain high levels of AR protein. We examined the in vitro effect of dihydrotestosterone (DHT) on DNA synthesis and progesterone secretion by follicular cells in response to FSH and IGF-1, alone or in combination. Cells from separate pools of 1-3 mm and 3-5 mm antral follicles were aspirated from gilt ovaries and fractioned into mural granulosa cells (MGCs) and cumulus-oocyte complexes (COCs) for subsequent cell culture. Androgen alone or with any combination of mitogen, had minimal effect on proliferative and no effect on steroidogenic responses of MGCs from 3-5mm antral follicles. Conversely, in MGCs from 1-3mm follicles, DHT significantly enhanced IGF-1 stimulated proliferation and had variable influence on progesterone secretion. The effects of DHT on proliferative responses of COC were also dependent on follicle size: DHT significantly augmented either IGF-1 stimulated proliferation (1-3mm follicles) or FSH- stimulated proliferation (3-5mm follicles). However, the steroidogenic responses of all COC were identical, whereby DHT significantly suppressed progesterone secretion, predominantly in the presence of FSH. Addition of an AR antagonist, hydroxyflutamide, generally reversed the proliferative responses invoked by DHT but not the steroidogenic responses. We conclude that androgen-receptor mediated activity in granulosa cells of antral follicles is dependent on follicle size, is influenced by proximity of cells to the oocyte, and possibly involves both classic and non-classic steroid mechanisms.

Key words: Androgen receptor • Cumulus cells • Follicular development • Granulosa cells • Growth factors

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