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 brain allopregnanolone, the most potent steroid produced by neurons, on ovulation rate and sexual behavior in female rats. Allopregnanolone was injected intracerebroventricularly in rats on diestrus and proestrus and tests were done on estrus. The intracerebroventricular injection of allopregnanolone significantly decreased the number of oocytes collected on estrus (p < 0.01). To support a physiological involvement, antiserum to allopregnanolone was injected centrally to block the activity of the endogenous neurosteroid. When administered on diestrus and proestrus 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 lordosis intensity was augmented significantly as compared to controls. Finally, the possible changes of medial basal hypothalamus concentration of allopregnanolone throughout the estrous cycle and at the time of ovulation were investigated. Hypothalamic extracts were eluted on high-pressure liquid chromatography and allopregnanolone concentration was measured by radioimmunoassay. Brain cortex was used as control tissue. Hypothalamic allopregnanolone concentration on proestrus morning and afternoon was found to be significantly lower than in the remaining phases of the estrous cycle (p < 0.01), while no significant changes were observed in brain cortex concentration of allopregnanolone. The present results suggest that hypothalamic allopregnanolone may be involved in the mechanism of ovulation, affecting hormonal and behavioral events.