The objective of the research outlined in this proposal is the elucidation of the mechanism(s) underlying sex differences in behavioral and hormonal responsiveness to the steroid hormones estrogen and progesterone. The endpoints to be measured are two physiological events triggered by these steriods, namely the expression of sexual receptivity (lordosis) and the stimulation of luteinizing hormone (LH) secretion. The data obtained will enhance our understanding of the basic cellular mechanisms by which steroid hormones exert effects on the central nervous system, and contribute to our knowledge of the sexual differentiation of these mechanisms. The focus of the experiments is on the regulation of the concentration of steroid hormone receptors in specific brain nuclei and the participation of the serotonergic system in determining responsiveness to steroid hormones. The adult male and female rat will be studied, as will the lightly androgenized female rat, as it exhibits a loss of responsiveness to steroid hormones, as it progresses from a state of estrous cyclicity to one of anovulation. A novel steroid hormone regimen, capable of inducing progesterone-facilitated lordosis in gonadectomized males and females, will be used to test the hypothesis that the induction of cytosol progestin receptors in specific nuclei of the brain is sexually differentiated, as some investigators have claimed. Furthermore, the ability of this hormone treatment to trigger LH surges in males and anestrous, androgenized females will be evaluated. Since serotonin activity has been reported to tonically inhibit the expression of lordosis in males, a combination of pharmacological and lesion techniques will be used to study the effects of manipulation of the central serotonergic system on steroid-induced lordosis, LH secretion and the concentration of steroid hormone receptors in specific brain nuclei which mediate the effects of steroids on sexual behavior and LH secretion. Finally, sex differences in the effects of steroid hormones on the concentration of serotonin receptors and anatomical colocalization of serotonin-containing neurons and steroid- accumulating cells in the brain will be evaluated, in order to elucidate interactions between these two, which may be responsible for sex differences in responsiveness to steroid hormones.
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