The long-term goal is to gain greater understanding of the role of the human and subhuman primate fetal gonad in sexual development. As an intermediate step leading to this goal, a series of in vitro and in vivo studies are planned. In vitro, it is proposed to study: 1) factors influencing growth of the fetal gonad by assessing the effects of epidermal growth factor, fibroblast growth factor, serum and placental extract on gonadal cell proliferation; 2) binding of gonadotropins to the fetal gonads and correlation of this binding with functional activity of the gonads; 3) facets of hCG formation by the human fetus, including synthesis by the fetal gonad, binding to fetal thyroid membranes and separation of fetal from placental hCG; and 4) possible factors responsible for the apparent lack of desensitization of fetal leydig cells by hCG. In vivo, in the long-term catheterized rhesus monkey fetus, it is proposed to determine: 1) whether there is pulsatile discharge of LH and FSH; 2) the effects of pulsatile administration of gonadotropin-releasing hormone on gonadotropin and gonadal steroid production; and 3) the possible modulating effects of opiate peptides and other modulators on gonadotropin production. As gonadal function, at least of the testis, is necessary for normal sexual development, and as gonadotropin-gonadal interactions differ significantly between primates and other experimental animals, greater understanding of these phenomena in the primate has significant biomedical relevance.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD018726-01A2
Application #
3315866
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1987-01-01
Project End
1989-12-31
Budget Start
1987-01-01
Budget End
1987-12-31
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Rabinovici, J; Spencer, S J; Doldi, N et al. (1992) Activin-A as an intraovarian modulator: actions, localization, and regulation of the intact dimer in human ovarian cells. J Clin Invest 89:1528-36
Rothman, P A; Chao, V A; Taylor, M R et al. (1992) Extraplacental human fetal tissues express mRNA transcripts encoding the human chorionic gonadotropin-beta subunit protein. Mol Reprod Dev 33:1-6
Rabinovici, J; Goldsmith, P C; Roberts, V J et al. (1991) Localization and secretion of inhibin/activin subunits in the human and subhuman primate fetal gonads. J Clin Endocrinol Metab 73:1141-9
Rabinovici, J; Jaffe, R B (1990) Development and regulation of growth and differentiated function in human and subhuman primate fetal gonads. Endocr Rev 11:532-57
Tapanainen, J; Voutilainen, R; Jaffe, R B (1989) Low aromatase activity and gene expression in human fetal testes. J Steroid Biochem 33:7-11
Huhtaniemi, I T; Yamamoto, M; Ranta, T et al. (1987) Follicle-stimulating hormone receptors appear earlier in the primate fetal testis than in the ovary. J Clin Endocrinol Metab 65:1210-4
Dumesic, D A; Goldsmith, P C; Jaffe, R B (1987) Estradiol sensitization of cultured human fetal pituitary cells to gonadotropin-releasing hormone. J Clin Endocrinol Metab 65:1147-53