The long-term objective of this research is to elucidate multihormonal mechanisms which control male reproductive functions. During the next five years we will examine the role of growth hormone (GH) in this process and, specifically, the effects of endogenous GH on the release of gonadotropins and prolactin (PRL). We will neutralize endogenous GH by injection of specific high titer antisera or by administration of somatostatin and examine the effects of these treatments on plasma levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and PRL, on the turnover of catecholamines in different regions of the hypothalamus, and on hypothalamic and pituitary function in vitro. Using similar approaches, we will evaluate the effects of GH treatment in genetically GH-deficient and in somatostatin-treated animals on the hypothalamus and the pituitary. The suspected cause:effect relationships between the changes in hypothalamic neurotransmitters and in pituitary hormonal release will be probed using various agonists, antagonists and precursors of dopamine and norepinephrine. Incubations and perifusions of hypothalamic and pituitary tissue with GH and insulin-like growth Factor-I (IGF-1) will be used to distinguish between direct and IGF-1 mediated actions of GH and to identify the site(s) of GH action. Additional experiments will address the suspected role of GH in the control of gonadotropin release by gonadal steroid feedback and in 'sexual maturation. Methods used for this research will include generation and characterization of antisera, radioimmunoassay measurements of pituitary and hypothalamic hormones, high performance liquid chromatography measurements of brain dopamine, norepinephrine and their metabolites, neuropharmacological studies, microdissection of brain tissues and breeding of mutant animals with hereditary GH deficiency. The results will answer whether physiological actions of GH include control of LH, FSH and PRL release and identify the mechanisms involved. This information is important for assessing the potential for undesirable side effects of GH treatment in medicine and in the animal industry.
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