REGULATION OF OVARIAN FOLLICULAR STEROID PRODUCTION

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During the follicular phase the capacity of preovulatory follicles to produce androgens and estradiol increases greatly, whereas progesterone secretion remains low. In vivo the LH/FSH surge triggers several dramatic and important changes, including the follicular/luteal phase shift in steroidogenesis. During this transition, follicular production of estradiol and androgen decrease greatly and theca and granulosa cells shift to primarily progesterone production - i.e., the transformation of follicle cells to luteal cells is initiated. Despite the critical importance of this phase of follicular development to successful reproduction, little is known about the mechanisms by which the follicular/luteal phase shift is accomplished, perhaps because the changes are so rapid. Oxytocin (OT) is produced by granulosa cells from humans and a number of other mammalian species, including cattle. Experiments conducted during the current grant period suggest that in cattle OT is involved in the mechanism by which the LH surge induces the initial stages of luteinization. Cattle offer unique advantages as a model for studying regulation of the follicular/luteal phase shift in mammals because: they can be induced experimentally to initiate luteal regression and a new follicular phase; large numbers of granulosa and theca cells can be obtained from a single follicle; and behavioral estrus serves as marker for the time of the LH/FSH surge. Therefore cattle will be used to determine mechanisms of the follicular/luteal phase shift, to gain insight into this important developmental transition and to explore the role of a proposed novel regulator, OT. Aim 1 is to determine the relationship between gonadotropins and OT in increasing progesterone secretion by bovine granulosa cells, to test the hypothesis that at least part of the mechanism by which the gonadotropins "luteinize" granulosa cells is via an increase in OT production. Aim 2 is to determine how luteinization is accomplished in vivo and in vitro in terms of expression of the genes for OT and specific steroidogenic enzymes. Experiments in Aim 3 will be focused on spontaneous luteinization iv vitro to examine mechanisms by which gonadotropins and OT "luteinize" cells in vitro. In Aim 4 the role of estradiol as a regulator of luteinization will be evaluated. The exciting new technique of follicular microdialysis will be used in Aim 5 to test hypotheses about the roles of LH and OT in the follicular/luteal phase shift in vivo. Together these experiments will provide new insight into the regulation of this transitional stage in follicular development that is so critical for fertility.