There are two main objectives to the research outlined in this application. The neural processes by which steroid hormones act to regulate female rodent sexual behavior will be studied. In addition, the relationship between steroid hormone-sensitive cells and neurotransmitterswill be investigated. The experiments in this proposal will add to our understanding of the cellular mechanisms by which the sex steroid hormones act on the central nervous system. The research makes use of a multidisciplinary approach including techniques of endocrinology, behavior, neuroanatomy and neuropharmacology. These experiments will require that some state-of-the-art neuroanatomical techniques be learned including immunocytochemistry and steroid autoradiography. These techniques will then be applied to the study of neurotransmitter-hormone interactions. Progesterone's effect on lordosis is used as a model neuroendocrine system, because progesterone has a unique, biphasic effect on this behavior, and because lordosis is a reliable, easily quantified, biologically-relevent, behavioral end-point of hormone action. In gonadectomized female rodents, progesterone synergizes with estradiol and induces a subsequent desensitization to progesterone. The role of the progestin receptor system in mediating progesterone's effects on this behavior, the regulation of the progestin receptor system, as well as an alternative mechanism of action for progesterone will be studied. The hypothesis that progesterone's desensitization effect, like its facilitatory effect, is involved in the regulation of sexual behavior during the estrous cycle of rodents will also be tested. Experiments to study the modulation of neural steroid hormone receptors by neurotransmitters are also described. These experiments are designed to study the regulation of steroid hormone receptors by neurotransmitters and of the neuroanatomical relationships involved in this regulation. Using a variety of neuroanatomical techniques, some characteristics of the cells that interact with estrogen- and progestin-sensitive cells will be determined. The hypothesis, that the regulation of steroid hormone receptors by neurotransmitters has functional significance for behavior, will be tested. The question of which neurotransmitters are present in progestinsensitive cells will also be studied.
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