The objectives of this research are to understand the actions of gonadal steroids on androgen and estrogen receptors in the brain that control male sexual behavior. The Syrian hamster is an appropriate animal model for these studies beacuse the male is dependent upon both chemosensory stimuli and gonadal hormones to elicit mating, and the basic pathways through the brain that mediate this behavior are known. Olfactory and vomeronasal chemosensory stimuli are processed through a chain of neurons that selectively take up androgens and estrogens from the bloodstream, and both of these signals (odors and hormones) are essential for normal mating to occur. Our preliminary studies have described the locations of steroid receptor- containing neurons and the repartitioning of the receptor from nucleus to cytoplasm after hormone withdrawal using immunocytochemistry. In the first Specific Aim, we will determine essential neurobiological mechanisms by which gonadal hormones stimulate copulation through autoregulation of their receptor. First, we will determine how androgens influence the levels of their receptor in the brain using in situ hybridization and receptor binding to quantify androgen receptor mRNA and protein in brains of gonad-intact and castrate males. Secondly, the time-course and dose- response to testosterone activation of neural andogen receptors will be determined using immunocytochemistry. Finally, we will localize unbound cytoplasmic androgen receptor at the ultrastructural level within neurons of castrated males.
In Specific Aim 2, we will focus on functional populations of androgen and estrogen receptor-containing neurons controlling sexual behavior. In particular, our studies will focus on the medial amygdaloid nucleus (Me), bed nucleus of the stria terminalis (BNST), and the medial preoptic area (MPOA) as potential sites for the integration of chemosensory and hormonal signals for copulation. We will determine the role of neonatal steroid exposure in the sexually dimorphic pattern of androgen receptors in MPOA. In addition, colocalization of androgen and estrogen receptor immunoreactivity will determine if individual neurons can respond to both gonadal steroids. Finally, we will use intracerebral implants of estrogen and DHT in Me and MPOA to determine the identity (androgen or estrogen) of steroid signals that induce copulation in these brain areas. The proposed studies have significance to understanding neural function under the influence of anabolic steroids. Abuse of these substances is becoming a serious health problem in our society. These observations on the location and hormonal regulation of androgen receptors in the brain will provide an essential basis for studying the behavioral effects of exogenous androgens.
| Coolen, L M; Wood, R I (1998) Bidirectional connections of the medial amygdaloid nucleus in the Syrian hamster brain: simultaneous anterograde and retrograde tract tracing. J Comp Neurol 399:189-209 |
