The long-term objectives of the proposed research are to develop a better understanding of a) cellular functions and interactions in the ovary and b) the role ovarian somatic cells have in the maintenance and control of ovarian functions. Specifically, the functions of granulosa cells and theca cells will be examined. In addition, interactions between these two cell types which are mediated via soluble peptides will be investigated.
Three specific aims are proposed: 1) to characterize appropriate markers (specific secreted proteins) of granulosa cell function and cytodifferentiation; 2) to analyze the control of granulosa cell function and cytodifferentiation; 3) to characterize factors produced by theca (i.e. stromal) cells that act on granulosa cells to regulate growth, function and cytodifferentiation. Proteins of interest will be isolated from serum-free conditioned medium obtained from primary cultures of rat granulosa cells or theca cells. These proteins will be purified by high pressure liquid chromatographic procedures and antibodies will be produced to the proteins. The influence of hormones and paracrine factors, derived from theca cells, have on the production of specific proteins secreted by granulosa cells will be used as a functional analysis. Granulosa cell cytodifferentiation will be investigated through an analysis of the effects of regulatory agents on the production of secreted and cellular proteins. The results of the proposed research will provide information on 1) the functions of granulosa cells and theca cells, 2) theca-granulosa cell interactions, 3) the hormonal control of these cellular functions and interactions, and 4) the influence of these cellular functions and interactions on the maintenance and control of oogenesis and folliculogenesis. In addition, these investigations will provide insight into general mesenchymal-epithelial cell interactions which occur in most organs such as the prostate, mammary gland, kidney and testis.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD020922-01A2
Application #
3319401
Study Section
Reproductive Biology Study Section (REB)
Project Start
1987-04-01
Project End
1990-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37203
Parrott, J A; Whaley, P D; Skinner, M K (1993) Extrahepatic expression of fibrinogen by granulosa cells: potential role in ovulation. Endocrinology 133:1645-9
Gettins, P; Dyal, D; Crews, B (1992) Selenium-dependent glutathione peroxidases from ovine and bovine erythrocytes occur as longer chain forms than previously recognized. Arch Biochem Biophys 294:511-8
Roberts, A J; Skinner, M K (1991) Transforming growth factor-alpha and -beta differentially regulate growth and steroidogenesis of bovine thecal cells during antral follicle development. Endocrinology 129:2041-8
Roberts, A J; Skinner, M K (1990) Hormonal regulation of thecal cell function during antral follicle development in bovine ovaries. Endocrinology 127:2907-17
Roberts, A J; Skinner, M K (1990) Estrogen regulation of thecal cell steroidogenesis and differentiation: thecal cell-granulosa cell interactions. Endocrinology 127:2918-29
Skinner, M K; Coffey Jr, R J (1988) Regulation of ovarian cell growth through the local production of transforming growth factor-alpha by theca cells. Endocrinology 123:2632-8
Skinner, M K; Osteen, K G (1988) Developmental and hormonal regulation of bovine granulosa cell function in the preovulatory follicle. Endocrinology 123:1668-75
Skinner, M K; Keski-Oja, J; Osteen, K G et al. (1987) Ovarian thecal cells produce transforming growth factor-beta which can regulate granulosa cell growth. Endocrinology 121:786-92
Skinner, M K; Lobb, D; Dorrington, J H (1987) Ovarian thecal/interstitial cells produce an epidermal growth factor-like substance. Endocrinology 121:1892-9