Effects of progestins on the estradiol-related accumulation of astrocytic granules in the hypothalamic arcuate nucleus

Adult female rats treated with a single 2 mg injection of estradiol valerate (EV) develop anovulatory sterility (persistent estrus) and neuropathologic changes in the hypothalamic arcuate nucleus. A prominent feature of the latter is the accumulation of peroxidase-positive cytoplasmic inclusions in arcuate astrocytes which results from aberrant patterns of chronic, ovarian E 2 secretion in this model. In the present study, we tested an hypothesis that progesterone may antagonize the pathologic effects of E 2 within the medial basal hypothalamus analogous to effects in peripheral steroid target tissues. In intact EV-treated rats, we observed complete suppression of the astrocytic reaction by subsequent injections of medroxyprogesterone acetate (MPA). However, chronic progesterone exposure did not significantly antagonize this estrogenic affect in ovariectomized rats implanted subcutaneously with steroid-releasing Silastic capsules. Taken together, these results suggest that progestins may block the development of an E 2-related arcuate lesion by suppressing the pituitary-ovarian axis rather than by directly antagonizing the dystrophic effects of E 2 at the hypothalamic level.