Ovarian folliculogenesis entails proliferation as well as differentiation of the developing granulosa cell (GC). Although the central role of gonadotropins in this process is well established, the variable fate of follicles afforded comparable gonadotropic stimulation, suggests the existence of additional intraovarian modulatory mechanism(s). Amongst potential novel modulators of GC ontogeny, Somatomedin-C appears uniquely suited to the task, combining replicative and cytodifferentiative properties. Although Sm-C was previously shown to stimulate bovine GC proliferation, the reciprocal nature of proliferation and differentiation precluded demonstration of its cytodifferentiative potential. To overcome this limitation, preliminary studies reported herein made use of rat GCs of limited growth potential in vitro, thereupon revealing that Sm-C is capable of synergizing with FSH in the induction of progesterone biosynthesis and LH receptors. Significantly, this direct cytodifferentiative effect of Sm-C is distinct from its replicative property, and may thus represent a novel biologic effect of this polypeptide. These observations, coupled with the demonstration of GC immunoreactive Sm-C release, suggest the existence of a novel intraovarian autocrine control mechanism, wherein Sm-C may serve as the central signal, and the granulosa cell its site of production, reception, and action. According to this view, Sm-C of GC origin may play an autocrine role at or adjacent to its site of synthesis, interacting with GC """"""""autoreceptors"""""""" to amplify or attenuate gonadotropic control of GC ontogeny. To test this hypothesis, in vitro studies are proposed on the role and regulation of GC immunoreactive Sm-C release, the characteristics and regulation of GC Sm-C receptors, as well as the mechanism(s) and site(s) of action of Sm-C in GC differentiation. In these experiments, the role(s) of endogenously produced Sm-C will be deduced from immunoneutralization studies, using a monoclonal antibody to Sm-C. Similarly, the indentity of the receptor mediating the cytodifferentiative effect of SM-C, will be evaluated through selective blockade of Sm-C receptors with an antireceptor monoclone. The long term objectives of this investigation include studies of the in vivo ontogeny of ovarian Sm-C and its receptor, the identification of ovarian Sm-C-producing cells other than the GC, the role of Sm-C in intraovarian paracrine interaction, and its linkage with defined physiologic processes.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD019998-02
Application #
3317740
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1985-04-01
Project End
1988-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201
deMoura, M D; Chamoun, D; Resnick, C E et al. (2000) Insulin-like growth factor (IGF)-I stimulates IGF-I and type 1 IGF receptor expression in cultured rat granulosa cells: autocrine regulation of the intrafollicular IGF-I system. Endocrine 13:103-10
Hourvitz, A; Widger, A E; Filho, F L et al. (2000) Pregnancy-associated plasma protein-A gene expression in human ovaries is restricted to healthy follicles and corpora lutea. J Clin Endocrinol Metab 85:4916-20
Kol, S; Ruutiainen-Altman, K; Scherzer, W J et al. (1999) The rat intraovarian interleukin (IL)-1 system: cellular localization, cyclic variation and hormonal regulation of IL-1beta and of the type I and type II IL-1 receptors. Mol Cell Endocrinol 149:115-28
Resnick, C E; Fielder, P J; Rosenfeld, R G et al. (1998) Characterization and hormonal regulation of a rat ovarian insulin-like growth factor binding protein-5 endopeptidase: an FSH-inducible granulosa cell-derived metalloprotease. Endocrinology 139:1249-57
Ando, M; Kol, S; Kokia, E et al. (1998) Rat ovarian prostaglandin endoperoxide synthase-1 and -2: periovulatory expression of granulosa cell-based interleukin-1-dependent enzymes. Endocrinology 139:2501-8
Ben-Shlomo, I; Kol, S; Roeder, L M et al. (1997) Interleukin (IL)-1beta increases glucose uptake and induces glycolysis in aerobically cultured rat ovarian cells: evidence that IL-1beta may mediate the gonadotropin-induced midcycle metabolic shift. Endocrinology 138:2680-8
Choi, D; Rohan, R M; Rosenfeld, R G et al. (1997) Activin-attenuated expression of transcripts encoding granulosa cell-derived insulin-like growth factor binding proteins 4 and 5 in the rat: a putative antiatretic effect. Biol Reprod 56:508-15
Kol, S; Ben-Shlomo, I; Ando, M et al. (1997) Insulin-like growth factor I affects the intraovarian interleukin-1 system: evidence for suppression of type I interleukin-1 receptor expression and enhancement of secretory phospholipase A2 expression and activity. Mol Hum Reprod 3:1095-9
Kol, S; Ruutiainen-Altman, K; Ben-Shlomo, I et al. (1997) The rat ovarian phospholipase A2 system: gene expression, cellular localization, activity characterization, and interleukin-1 dependence. Endocrinology 138:322-31
Adashi, E Y; Resnick, C E; Payne, D W et al. (1997) The mouse intraovarian insulin-like growth factor I system: departures from the rat paradigm. Endocrinology 138:3881-90

Showing the most recent 10 out of 80 publications