Our primary goal is to learn about the basic neuroendocrine mechanisms controlling the reproduction in the male primate. We propose to use in situ hybridization for GnRH mRNA to study the physiological control of GnRH gene expression within individual neurons in the brain of the male macaque, Macaca fascicularis. We have plotted 4 major areas of investigation. The first concerns steroid hormone feedback. Testosterone serves a major role in the feedback control of GnRH secretion in the male primate, but the cellular mechanisms mediating this process remain obscure. In this aspect of the proposal, we will focus on determining whether gonadal hormones, and testosterone in particular, influence the level of GnRH mRNA in the brain; in addition, we will attempt to ascertain whether endogenous opioid pathways are involved in this negative feedback system. The second part concerns development. In primate species, the maturation of the reproductive system awaits only the augmentation of GnRH secretion, but the cellular mechanisms underlying the pubertal awakening of GnRH secretion are still unresolved. In this aspect of the proposal, we will focus on determining whether increases in GnRH mRNA can be implicated in controlling the onset of puberty in the primate. The third part concerns the problem of metabolic stress. Nutritional and metabolic status can have a profound influence on the secretion of GnRH in primates, but again, the cellular mechanisms mediating these disturbances remain unknown. We will attempt to ascertain whether changes in GnRH mRNA are responsible for changes in GnRH secretion caused by alterations in metabolism and to elucidate the possible role of glucocorticoids and corticotropin-releasing hormone in this process. Fourth, we will try to improve the methodology for conducting in situ hybridization analysis of GnRH mRNA in the brain. We believe this work will foster a better understanding of basic cellular neurobiology and help us to understand more about clinical problems related to human reproduction.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD012625-11
Application #
3311940
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1979-04-01
Project End
1992-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
11
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Christensen, R B; Forage, R G; Steiner, R A et al. (1994) Effects of castration and recombinant human inhibin administration on circulating levels of inhibin and gonadotropins in adult male monkeys. J Androl 15:125-31
Delemarre-van de Waal, H A; Burton, K A; Kabigting, E B et al. (1994) Expression and sexual dimorphism of galanin messenger ribonucleic acid in growth hormone-releasing hormone neurons of the rat during development. Endocrinology 134:665-71
Bergendahl, M; Wiemann, J N; Clifton, D K et al. (1992) Short-term starvation decreases POMC mRNA but does not alter GnRH mRNA in the brain of adult male rats. Neuroendocrinology 56:913-20
Burton, K A; Kabigting, E B; Clifton, D K et al. (1992) Growth hormone receptor messenger ribonucleic acid distribution in the adult male rat brain and its colocalization in hypothalamic somatostatin neurons. Endocrinology 131:958-63
Soules, M R; Bremner, W J; Steiner, R A et al. (1991) Prolactin secretion and corpus luteum function in women with luteal phase deficiency. J Clin Endocrinol Metab 72:986-92
Bremner, W J; Bagatell, C J; Steiner, R A (1991) Gonadotropin-releasing hormone antagonist plus testosterone: a potential male contraceptive. J Clin Endocrinol Metab 73:465-9
Zeitler, P; Tannenbaum, G S; Clifton, D K et al. (1991) Ultradian oscillations in somatostatin and growth hormone-releasing hormone mRNAs in the brains of adult male rats. Proc Natl Acad Sci U S A 88:8920-4
Argente, J; Chowen, J A; Zeitler, P et al. (1991) Sexual dimorphism of growth hormone-releasing hormone and somatostatin gene expression in the hypothalamus of the rat during development. Endocrinology 128:2369-75
Adams, L A; Vician, L; Clifton, D K et al. (1991) Testosterone regulates pro-opiomelanocortin gene expression in the primate brain. Endocrinology 128:1881-6
Wiemann, J N; Clifton, D K; Steiner, R A (1990) Gonadotropin-releasing hormone messenger ribonucleic acid levels are unaltered with changes in the gonadal hormone milieu of the adult male rat. Endocrinology 127:523-32

Showing the most recent 10 out of 40 publications