The physiological mechanisms involved in the impairment of reproductive function by chronic stress are unknown. Results of several studies suggest that elevated levels of glucocorticoids can act to block growth and function of ovulatory follicles. The purpose of this proposal is to determine if stress induced by glucocorticoid treatment impairs reproductive function at the ovarian level or at hypothalamic-hypophyseal axis. We will study two common forms of ovarian dysfunction 1) blockade of ovulatory follicle recruitment and 2) induction of cystic follicles. Both forms of ovarian dysfunction will be induced in female pigs by dexamethasone treatment during the luteal and follicular phases, respectively. Follicular fluid and ovarian tissue will be analyzed to study the effects of dexamethasone at the ovarian level. For studies involving blockage of ovulatory follicle recruitment, ovaries will be collected during the early and late follicular phase. In the ovarian cyst study, ovaries will be collected during the late follicular phase and the early luteal phase of the next cycle. One ovary will be used to determine the degree to which ovarian follicular fluid steroid hormone concentrations are correlated with the proportion of follicles with normal, cystic or atretic morphology. To establish the molecular site of regulation by dexamethasone, frozen sections of the other ovary will be analyzed by immunohistochemistry and by in situ hybridization. Changes in the expression of steroidogenic enzymes, gonadotropin receptors, and in the ovarian insulin-like growth factor system will be correlated with indices of cell death and proliferation. Frequent blood sampling will be undertaken during the experiments to determine if the pulsatile nature of LH is altered by dexamethasone treatment. Pituitaries will be analyzed to determine if dexamethasone suppresses gonadotropin content and the expression of mRNA for LH and FSH subunits. These studies will improve the understanding stress effects on ovarian physiology and dysfunction.
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