EVIDENCE FOR A ROLE FOR THE NEUROSTEROID ALLOPREGNANOLONE IN THE MODULATION OF REPRODUCTIVE FUNCTION IN FEMALE RATS

The present study investigated the effect of allopregnanolone (5 alpha -pregnan-3 alpha-ol-20-one) or of passive immunoneutralization of brai n allopregnanolone, the most potent steroid produced by neurons, on ov ulation rate and sexual behavior in female rats. Allopregnanolone was injected intracerebroventricularly in rats on diestrus and proestrus a nd tests were done on estrus, The intracerebroventricular injection of allopregnanolone significantly decreased the number of oocytes collec ted on estrus (p < 0.01). To support a physiological involvement, anti serum to allopregnanolone was injected centrally to block the activity of the endogenous neurosteroid. When administered on diestrus and pro estrus or only on proestrus, the antiserum was shown to be correlated with a significant increase (p < 0.01) in oocytes retrieved on estrus. In female rats treated with antiserum to allopregnanolone, the lordos is intensity was augmented significantly as compared to controls, Fina lly, the possible changes of medial basal hypothalamus concentration o f allopregnanolone throughout the estrous cycle and at the time of ovu lation were investigated. Hypothalamic extracts were eluted on high-pr essure liquid chromatography and allopregnanolone concentration was me asured by radioimmunoassay. Brain cortex was used as control tissue. H ypothalamic allopregnanolone concentration on proestrus morning and af ternoon was found to be significantly lower than in the remaining phas es of the estrous cycle (p < 0.01), while no significant changes were observed in brain cortex concentration of allopregnanolone, The presen t results suggest that hypothalamic allopregnanolone may be involved i n the mechanism of ovulation, affecting hormonal and behavioral events .