In contrast to the stimulatory or permissive effects of growth hormone (GH) on sexual development and adult gonadal function, excessive secretion of GH in the human is associated with reproductive impairments including amenorrhea and impotence. Experimentally-induced GH excess in transgenic mice is associated with severe deficits of male sexual behavior. In the proposed studies, several potential mechanisms of the suppressive effects of GH on male copulatory behavior will be examined. The relationship between plasma GH levels and male copulatory behavior will be examined. The relationship between plasma GH levels and male copulatory behavior will be examined in two lines of transgenic mice in which expression of the bGH gene will be enhanced or suppressed (by heavy metal supplement, and altered diet, respectively) and in genetically normal mice chronically infused with bGH. The possible involvement of altered adrenocortical or testicular function in mediating the effects of GH on behavior will be assessed in studies of adrenalectomized and castrated animals given corticosterone or testosterone replacement. The effects of chronic GH excess on neuronal groups involved in perception of stimuli will be evaluated by studies of the """"""""early gene,"""""""" c-fos expression in different areas of the olfactory lobes and the hypothalamus after exposure of transgenic and normal control males to a novel female. The possible involvement of altered forebrain dopaminergic transmission, including the dopaminergic """"""""reward system"""""""" in mediating the effects of GH on male copulatory behavior will be evaluated in transgenic and normal males treated with agonists or antagonists of dopamine receptors. To determine whether the effects of GH on sexual behavior observed in the mouse may apply also to other species, comparative studies will be conducted in GH-treated male rats and hamsters. To determine whether the effects of excessive GH levels on copulatory behavior in transgenic and normal animals are related to the physiological role of the normally released amounts of this hormone, the effects of GH replacement on sexual behavior will be studied in hypophysectomized animals, in animals with hereditary GH deficiency and in animals with experimentally-induced suppression of GH release or action. The results of this research will be pertinent to understanding the reproductive and sexual dysfunction in patients with acromegaly, and the potential side effects of GH treatment during maturation, convalescence and aging.
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