Interaction between the hypothalamic-pituitary-adrenal axis (HPA) and the hypothalamic-pituitary-ovarian axis (HPO) is well established but best understood at the level of the central nervous system (CNS) where the adrenal axis has an inhibitory influence on the reproductive axis. Data from our preliminary studies and isolated observations from previously published work, however, indicate that glucocorticoids can, alternatively, enhance reproductive function, likely due to a direct effect of on the ovary. When dexamethasone was administered during the PMSG/hCG priming regimen to immature rats the result was an increase over controls in litter size, ova shed and number of preantral and antral follicles just prior to the endogenous LH surge. Because dexamethasone regulates both Bcl-2 proteins and IAPs in other cells and tissues we surmise that these particular intracellular proteins, mediators of apoptosis in the follicle, may be the key to deciphering how glucocorticoids effect follicular development. We hypothesize that the effect of dexamethasone in the ovary is to suppress atresia in antral follicles and thus increase the number of follicles that ovulate in response to hCG (endogenous analog for LH). The project will evaluate whether dexamethasone acts directly on the ovary to alter follicular development during the priming/treatment period such that a larger crop of follicles ovulates. Three studies will be conducted. The first will evaluate the number of healthy versus atretic ovarian follicle, at 3 stages of follicular growth, at 6 time points following either gonadotropin priming (controls) or gonadotropin priming in combination with dexamethasone treatment of animals. In a second series of studies we will determine whether dexamethasone's effects on ovulation are present in hypophysectomized animals. Finally, we will harvest ovarian tissue from which to extract total RNA to assay mRNA expression of Bcl-2 genes from control and DEX treated animals. If dexamethasone treatment alters Bcl-2 mRNA expression in the rat ovary we will examine protein expression and localization using western blot analysis and immunocytochemistry.
NIH ExPorter
NIH ExPorter