The hypothalamus and limbic brain play an important role in the regulation of gonadotropin secretion and reproductive behavior in the male. Numerous pharmacological studies have suggested a major role for monoaminergic neurons in mediating aspects of both of these processes. There is, however, a complex interaction between androgens and neurotransmitters within the brain. Not only do changes in neurotransmission affect androgen-dependent processes, but changes in the levels of circulating testosterone can affect some processes relating to catecholamine transmission. This grant proposes to study these aspects of the cellular mechanism of androgen action by determining (1) whether monoamines affect the metabolism of androgens to active estrogenic metabolites (aromatization) in the brain; and (2) whether testosterone (T) or its active metabolites, in turn, regulate the number and/or affinity of dopamine (D2) receptors in regions of the brain relevant to behavioral and neuroendocrine functions. To accomplish the first objective, experiments are outlined that will measure aromatase activity and nuclear androgen receptor concentrations under conditions where monoamine dynamics have ben altered by agonists, antagonists, and synthesis blockers. The second goal will be approached with studies that will measure the binding parameters of dopamine (D2) receptors in male rats after various endocrine manipulations that will vary the androgen status on the animals. Pharmacologic intervention will be used to dissect out the contribution made by active T metabolites. Finally, studies are proposed which will begin to localize androgen modulated catecholamine binding within specific hypothalamic nuclei. This studies proposed herein will lead to a better understanding of how androgens interact with neurotransmitters to regulate neuronal functions. Moreover the information gained should add to our knowledge to the central components in the physiology and pathophysiology of male reproduction and sexual development. In a larger sense, this research has implications for our understanding of the cellular events underlying the action of all gonadal steroids

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HD023293-04
Application #
3469657
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1987-07-01
Project End
1992-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
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Roselli, C E; Thornton, J E; Chambers, K C (1993) Age-related deficits in brain estrogen receptors and sexual behavior of male rats. Behav Neurosci 107:202-9
Roselli, C E; Resko, J A (1993) Aromatase activity in the rat brain: hormonal regulation and sex differences. J Steroid Biochem Mol Biol 44:499-508
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Chambers, K C; Thornton, J E; Roselli, C E (1991) Age-related deficits in brain androgen binding and metabolism, testosterone, and sexual behavior of male rats. Neurobiol Aging 12:123-30
Roselli, C E (1991) Sex differences in androgen receptors and aromatase activity in microdissected regions of the rat brain. Endocrinology 128:1310-6
Roselli, C E (1991) Synergistic induction of aromatase activity in the rat brain by estradiol and 5 alpha-dihydrotestosterone. Neuroendocrinology 53:79-84
Roselli, C E; Kelly, M J; Ronnekleiv, O K (1990) Testosterone regulates progonadotropin-releasing hormone levels in the preoptic area and basal hypothalamus of the male rat. Endocrinology 126:1080-6
Kelly, M J; Garrett, J; Bosch, M A et al. (1989) Effects of ovariectomy on GnRH mRNA, proGnRH and GnRH levels in the preoptic hypothalamus of the female rat. Neuroendocrinology 49:88-97
Roselli, C E; Handa, R J; Resko, J A (1989) Quantitative distribution of nuclear androgen receptors in microdissected areas of the rat brain. Neuroendocrinology 49:449-53