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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD020001-12
Application #
2025110
Study Section
Reproductive Biology Study Section (REB)
Project Start
1984-07-01
Project End
1998-11-30
Budget Start
1996-12-01
Budget End
1997-11-30
Support Year
12
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Southern Illinois University Carbondale
Department
Physiology
Type
Schools of Medicine
DUNS #
939007555
City
Carbondale
State
IL
Country
United States
Zip Code
62901
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Srivastava, Vinod K; Dearth, Robert K; Hiney, Jill K et al. (2002) Alcohol suppresses insulin-like growth factor-1 gene expression in prepubertal transgenic female mice overexpressing the bovine growth hormone gene. Alcohol Clin Exp Res 26:1697-702
Gonzalez, L; Sotelo, A I; Bartke, A et al. (2001) Growth hormone (GH) and estradiol regulation of membrane-associated GH binding protein and GH receptors in GH releasing hormone transgenic mice. Growth Horm IGF Res 11:34-40
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Gonzalez, L; Sotelo, A I; Bartke, A et al. (1999) Up-regulation of GH-binding protein by mouse GH in transgenic mice overexpressing GH-releasing hormone. J Endocrinol 163:299-307
Debeljuk, L; Steger, R W; Wright, J C et al. (1999) Effects of overexpression of growth hormone-releasing hormone on the hypothalamo-pituitary-gonadal function in the mouse. Endocrine 11:171-9
Matthews, J C; Beveridge, M J; Dialynas, E et al. (1999) Placental anionic and cationic amino acid transporter expression in growth hormone overexpressing and null IGF-II or null IGF-I receptor mice. Placenta 20:639-50
Bartke, A; Chandrashekar, V; Turyn, D et al. (1999) Effects of growth hormone overexpression and growth hormone resistance on neuroendocrine and reproductive functions in transgenic and knock-out mice. Proc Soc Exp Biol Med 222:113-23
Dialynas, E; Brown-Borg, H; Bartke, A (1999) Immune function in transgenic mice overexpressing growth hormone (GH) releasing hormone, GH or GH antagonist. Proc Soc Exp Biol Med 221:178-83

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