The purpose of this application is to generate new information about the organizing actions of androgen at the cellular level on the brain of two long gestation mammals, the guinea pig and the rhesus monkey. Based on preliminary data, experiments are proposed which will carefully plot changes in the ontogeny of cytosolic androgen receptors (ARc) in the cortex and hypothalamus of these species at critical times in fetal development and relate these changes to the effects of androgen on sexual responsiveness and the capacity of males to release gonadotropins in a cyclic manner. Attempts will be made to systematically evaluate the technique for quantifying nuclear androgen receptors (ARn) since they can not be measured in fetal tissues by conventional means. The actions of tissue proteases on ARn destruction will be studied as well as possible localization within the nuclear matrix. Studies are proposed in which the role of brain aromatization in sexual differentiation will be ascertained by the use of aromatase inhibitors during pregnancy. In addition molecular probes have been obtained to study the ontogeny of mRNA for aromatase P-450 in the rhesus monkey fetus. Likewise, the capacity of exogenous testosterone to androgenize the cyclic centers that control gonadotropin release in the fetal guinea pig will be evaluated. These studies will provide new information on cellular events that mediate hormonal control of brain development.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD016022-10
Application #
3313389
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1981-05-01
Project End
1994-02-28
Budget Start
1991-03-01
Budget End
1992-02-29
Support Year
10
Fiscal Year
1991
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
Connolly, P B; Resko, J A (1994) Prenatal testosterone differentiates brain regions controlling gonadotropin release in guinea pigs. Biol Reprod 51:125-30
Connolly, P B; Choate, J V; Resko, J A (1994) Effects of exogenous androgen on brain androgen receptors of the fetal rhesus monkey. Neuroendocrinology 59:271-6
Choate, J V; Resko, J A (1994) Prenatal inhibition of aromatase activity affects luteinizing hormone feedback mechanisms and reproductive behaviors of adult guinea pigs. Biol Reprod 51:1273-8
Connolly, P B; Roselli, C E; Resko, J A (1994) Aromatase activity in developing guinea pig brain: ontogeny and effects of exogenous androgens. Biol Reprod 50:436-41
Toyooka, K T; Connolly, P B; Resko, J A (1991) Effects of exogenous steroids on androgen receptors in fetal guinea pig brain. Biol Reprod 44:1051-62
Resko, J A; Abdelgadir, S E; Connolly, P B (1991) Androgen metabolism by hepatic and renal tissues of the fetal rhesus monkey. J Steroid Biochem Mol Biol 38:513-21
Connolly, P B; Roselli, C E; Resko, J A (1990) Aromatase activity in adult guinea pig brain is androgen dependent. Biol Reprod 43:698-703
Abdelgadir, S E; Connolly, P B; Resko, J A (1990) Androgen binding in peripheral tissues of fetal rhesus macaques: effects of androgen metabolism in liver. J Steroid Biochem Mol Biol 37:545-51
Ronnekleiv, O K; Resko, J A (1990) Ontogeny of gonadotropin-releasing hormone-containing neurons in early fetal development of rhesus macaques. Endocrinology 126:498-511
Toyooka, K R; Connolly, P B; Handa, R J et al. (1989) Ontogeny of androgen receptors in fetal guinea pig brain. Biol Reprod 41:204-12

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