The long-term objective of the project is to provide a basic understanding of ovarian cellular gonadotropin receptor regulation which will eventually be applicable to the problem of fertility regulation. This application is concerned primarily with determining the chemical and biological characteristics of a factor which has been partially purified from platelet-derived growth factor (PDGF) preparations. This material facilitates differentiation by enhancing FSH-stimulated LH receptor induction in granulosa cells. It appears to be a unique species of human Transforming Growth Factor Beta which we are provisionally designating Transforming Growth Factor-Beta-Like Material (TGF-B-LM). To extend these findings, this proposal is concerned with three specific aims: 1) to elucidate the chemical properties of TGF-B-LM by a) purifying it to electrophoretic homogeneity, b) determining the amino acid sequence of the material by gas-phase microsequenator technology, and c) by generating antibodies to TGF-B-LM for application to purification procedures; 2) to investigate the biological properties of TGF-B- LM by a) analyzing in greater detail how TGF-B-LM potentiates FSH-stimulated induction of functional LH/hCG receptor, b) characterizing its growth-promoting or inhibiting properties upon primary cultures of granulosa or cumulus cells and ovarian cancer cell lines and c) utilizing TGF-B-LM and anti-TGF-B-LM immunoprecipitation approaches to determine whether ovarian cells themselves produce TGF-B-LM; 3) to isolate and identify an FSH- and EGF-modulated Mr 27,000 component from porcine granulosa cells and determine its principal physiological role.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD011827-10A1
Application #
3311674
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1978-04-01
Project End
1990-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
10
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Shang, W; Konidari, I; Schomberg, D W (2001) 2-Methoxyestradiol, an endogenous estradiol metabolite, differentially inhibits granulosa and endothelial cell mitosis: a potential follicular antiangiogenic regulator. Biol Reprod 65:622-7
Chun, S Y; McGee, E A; Hsu, S Y et al. (1999) Restricted expression of WT1 messenger ribonucleic acid in immature ovarian follicles: uniformity in mammalian and avian species and maintenance during reproductive senescence. Biol Reprod 60:365-73
Schomberg, D W; Couse, J F; Mukherjee, A et al. (1999) Targeted disruption of the estrogen receptor-alpha gene in female mice: characterization of ovarian responses and phenotype in the adult. Endocrinology 140:2733-44
Gitay-Goren, H; Kim, I C; Miggans, S T et al. (1993) Transforming growth factor beta modulates gonadotropin receptor expression in porcine and rat granulosa cells differently. Biol Reprod 48:1284-9
Mulheron, G W; Bossert, N L; Lapp, J A et al. (1992) Human granulosa-luteal and cumulus cells express transforming growth factors-beta type 1 and type 2 mRNA. J Clin Endocrinol Metab 74:458-60
Mulheron, G W; Mulheron, J G; Danielpour, D et al. (1992) Porcine granulosa cells do not express transforming growth factor-beta 2 (TGF-beta 2) messenger ribonucleic acid: molecular basis for their inability to produce TGF-beta activity comparable to that of rat granulosa cells. Endocrinology 131:2609-14
Tilly, J L; Kowalski, K I; Schomberg, D W et al. (1992) Apoptosis in atretic ovarian follicles is associated with selective decreases in messenger ribonucleic acid transcripts for gonadotropin receptors and cytochrome P450 aromatase. Endocrinology 131:1670-6
Mulheron, G W; Schomberg, D W (1992) Effects of diethylstilbestrol on rat granulosa cell and thecal/interstitial cell transforming growth factor-beta 2 mRNA expression in vivo: analysis by reverse transcription-polymerase chain reaction. Biol Reprod 46:546-50
Mulheron, G W; Danielpour, D; Schomberg, D W (1991) Rat thecal/interstitial cells express transforming growth factor-beta type 1 and 2, but only type 2 is regulated by gonadotropin in vitro. Endocrinology 129:368-74
Mulheron, G W; Schomberg, D W (1990) Rat granulosa cells express transforming growth factor-beta type 2 messenger ribonucleic acid which is regulatable by follicle-stimulating hormone in vitro. Endocrinology 126:1777-9

Showing the most recent 10 out of 18 publications