Regional sex differences in progestin receptor induction in the rat hypothalamus: effects of various doses of estradiol benzoate.

In the rat, sex differences in behavioral responsiveness to progesterone have been correlated with a sex difference in estrogen-induced progestin receptor induction in the ventromedial nucleus (VMN). It has recently been suggested that this sex difference in progestin receptor induction may only be present after treatment with large doses of estrogen. We have evaluated the sex difference in hypothalamic cytosol progestin receptor induction in gonadectomized/adrenalectomized rats treated with moderate doses of estradiol benzoate (EB; 20 micrograms/kg body weight). No sex differences were detected in cytosol progestin binding in mediobasal hypothalamus or preoptic area of animals treated with this dose 48 hr before they were killed. However, a higher level of progestin binding in the VMN of females than of males was found when these brain regions were examined using a microdissection technique. Saturation binding analysis of progestin binding in the VMN indicated that this sex difference in binding reflects a difference in the number of progestin binding sites, and not a difference in binding affinity. A dose-response study of progestin receptor induction in the medial preoptic nucleus (mPON), arcuate-median eminence region (ARC-ME), and VMN of male and female rats indicated a sex difference in cytosol progestin binding in the VMN at all EB doses tested (2, 8, 40, or 200 micrograms/kg body weight). No sex differences in cytosol progestin binding in the mPON or ARC-ME were observed at any of the tested doses. These results support the idea that the differences in behavioral sensitivity to progesterone may result in part from sex differences in the estrogen induction of progestin receptors in the VMN.