The proposed research will test the hypothesis that the gonadal steroid hormones, estradiol (E2) and progesterone (P) influence feminine sexual behavior and neuroendocrine physiology in rats by changing the number of neurotransmitter receptors in specific nuclei of the medial basal hypothalamus (MBH) and pre-optic area (POA), where E2 and P are known to produce behavioral and physiological effects. This is suggested by our recent finding that E2 treatment increases the number of muscarinic cholinergic receptors in steroid -concentrating nuclei of th MBH-POA. We will determine if the evaluation of muscarinic receptors by E2 is a necessary event in the induction of sexual behavior and LH release. This will be done by correlating the time course of the biochemical event with the time course of the activational effects of E2, by determining if specific inhibitors of lordosis behavior and LH release also inhibit the E2 induction of muscarinic receptors, and by attempting to block the activational effects of E2 by stereotaxically implanting muscarinic antagonists into MBH-POA nuclei. We will also examine the effects of gonadal steroids of Beta-adrenergic, opiate, GABA, glutamate and histamine receptors in MBH-POA nuclei. These neurotransmitter receptors have either been strongly implicated in steroids effects on behavior and LH release, or are present in high numbers in the nuclei where steroids produce these effects. In all cases, we will measure neurotransmitter receptors by specific radioligand binding methods on microdissected tissue from MBH-POA, and by quantitative autoradiography on brain sliced according to the in vitro method of Young and Kuhar (Brain Res. 179: 225-270, 1979). Our results on E2 induction of muscarinic receptors suggest that changing the number of neurotransmitter receptors in specific brain regions might be an important mechanism by which steroids modify synaptic function to activate behavioral and neuroendocrine events. An understanding of how gonadal steroids modify the molecular properties of synapses to alter neuronal function is necessary to devise improved treatments for diseases of neuroendocrine systems, and might clarify more complicated forms of synaptic plasticity, such as associative learning and memory formation.