the object of the proposed research is to continue our studies on the sites and mechanisms within the central nervous system in which estrogen and progesterone act to affect the preovulatory release of luteinizing hormone and prolactin. To this end we have proposed a series of studies to examine the interplay which exists between these sex steroids and changes in releasability of LHRH from median eminence axon terminals (synaptosomes) using a variety of experimental paradigms. We also propose to examine the duration of occupancy and concentrations of estrogen nuclear and progestin cytosol receptors required to elicit spontaneous LH and PRL surges in long and short term ovariectomized (OVX) rats and the effects of such receptor occupancy on releasability of synaptomsomal LHRH. Coupled with these studies will be an extensive investigation of the critical role that the catechol and indolamine systems exert on the LHRH system to trigger gonadotropin surges. To this end we will examine (a) the input of noradrenergic axons to specific preoptic and hypothalamic regions using electrical activation of the mid and hindbrain noradrenergic cell bodies and/or tegmental tracts; (b) effects of 5-HT on release of LHRH and how 5-HT turnover rates (T/R) change during proestrus and whether they affect norepinephrine (NE) T/R; (c) the effects of estrogen on mid and hindbrain function to activate or inhibit NE T/R in the hypothalamus. Using both estradiol and anti-estrogens we will microimplant these into POA, mid or hindbrain of OVX rats to learn if the LHRH vs NE systems can be independently affected so that LHRH synthesis or NE T/R can be selectively activated or inhibited. Finally, we will study whether puromycin (protein synthesis inhibitor) changes LHRH releasability or NE T/R after E2 treatment. This drug will be discretely placed in preoptic versus brain stem regions. Thus, the studies described in this proposal will examine the importance of the catechol and indol amine systems in triggering LH and PRL release, some of the neuronal and steroid nuclear events involved in this action and how estrogen and progesterone modify the function of both the LHRH and monoamine systems to activate or inhibit LH secretion.
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