In this application for an ADAMHA Research Career Development Award (Level II), salary support is requested to conduct experiments in the field of cellular mechanisms of hormone action in the brain and anatomy of hormone systems that regulate behavior. Regulation of the sexually-receptive posture, lordosis, in guinea pigs is used as a model, because the ovarian steroid hormones, estradiol and progesterone have interesting and well-studied interactions; estradiol increases behavioral response to progesterone, progesterone facilitates the expression of lordosis, and it then desensitizes the animal to further response. A variety of approaches from behavioral and neuroanatomical to molecular will be used to elucidate the anatomical and cellular mechanisms involved in estradiol and progesterone regulation of this hormonally-regulated, neurally-mediated behavior. Some of these include behavioral observation to determine the effects of particular hormonal, pharmacological and behavioral manipulations on this system, tract-tracing of afferent neurons and efferent targets of the cells in the hypothalamus that contain intracellular binding proteins for estradiol and progesterone. Immunocytochemistry will be used for labeling of steroid hormone receptors as well as for neurotransmitters and neuropeptides believed to be involved in the cellular actions of these hormones. In situ hybridization will be used to examine mRNA levels for these neurotransmitters and steroid hormone receptors. Electron microscopic techniques will be used to confirm ultrastructural relationships and to determine the subcellular localization of steroid hormone receptors in the brain.
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