The long term goal of this research is to elucidate the genomic pathways that facilitate lordosis and other female rat sexual behaviors. Specifically, this proposal is aimed at identifying estrogen- (E) and progesterone- (P) sensitive genes within the ventromedial hypothalamus (VMH) and addressing the question of whether or not they effect female sexual behaviors. For the identification of E- and P-sensitive genes, ovariectomized rats will be given physiological doses of E and P and the VMH harvested for RNA isolation, shortly before the expected peak onset of lordosis. To identify the sensitive genes, the differential display polymerase chain reaction will be used in conjunction with suppression subtraction CDNA library construction and screening. The hormone sensitivity of these genes will be confirmed by differential slot blotting and in situ hybridization analysis. These genes will be further explored in a naturally cycling environment using in situ hybridization studies on brains from intact female rats at diestrus and proestrus. Finally, antisense DNA studies will be performed to determine the effects of these genes on lordosis and other rat sexual behaviors. The proposed studies will help define the molecular mechanisms by which endocrine signals, in the form of E and P, facilitate a behavior the ensures reproduction of the species. Insights from these studies may also reveal how the ovarian hormones E and P effect human behavior.
