Steroid-Catecholamine Interactions and Behavior

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DESCRIPTION (provided by applicant): The goal of this research is to elucidate fundamental relationships among neurotransmitters, hormones, and brain function mediating the activation of appetitive and consummatory male sexual behavior in Japanese quail (Coturnix japonica). In particular the roles played by the catecholamine, dopamine (DA), and the testosterone (T) metabolizing enzyme, aromatase, in relation to the activation by T of male behaviors will be studied. The proposed work includes 12 experiments in 5 aims and capitalizes on findings concerning the neuroendocrine control of sexual behavior in quail that make this species a unique model for these studies. AIM I concerns the neural circuitry that controls the expression of sexual behavior and focuses on the specific projection of preoptic aromatase cells to the mesencephalic central gray (GCt). We will analyze the behavioral effects of estrogens produced in GCt (Exp 1) and a possible sex difference in the organization of this projection (Exp 2). AIM 2 will investigate the role of DA in the control of sexual behavior by analyzing the behavioral effects of central injections of DAergic drugs (Exp 3). AIM 3 will focus on the genomic mechanisms through which T controls the expression of male behavior and of aromatase activity (AA) by investigating sex differences in the expression of estrogen receptors (ERalpha and ERbeta) or of the steroid receptor coactivator-1 (SRC-1) (Exp 4) and analyzing the functional significance of SRC-1 by antisense techniques (Exp 5-6). AIM 4 focuses on rapid changes in AA mediated by phosphorylations and analyzes the reversibility of the aromatae inhibition by phosphorylations (Exp 7) and the contribution of excitatory amino acids to the control of rapid changes in AA (Exp 8). AIM 5 will investigate the effects of rapid variations in estrogen bioavailability due to fast changes in AA by -measuring the levels of 17beta estradiol (E2) present in aromatase cell groups (Exp 9), testing whether E2 rapidly affects the expression of male sexual behavior (Exp 10) as well as investigating rapid changes in the phosphorylation of CREB or tyrosine hydroxylase and tyrosine hydroxylase activity following exposure to E2 (Exp 11-12). These studies will provide new information about the interplay between steroid action and DAergic transmission in the activation of sexual behavior and thereby provide insight into the etiology of male sexual dysfunction and of sexually differentiated or steroid-dependent diseases.