The mammalian corpus luteum is a transient gland. During the menstrual or estrous cycle, it develops, secretes progesterone for a period of time characteristic of the species, and then declines. In the human and the cow, the tropic factors which regulate luteal function have been demonstrated to be predominantly luteinizing hormone (LH) and human chorionic gonadotropin. However, the mechanisms by which the effects of LH are propagated at the cellular and molecular level remain a mystery. It is well recognized that progesterone secretion is closely coupled to the ability of LH to increase cAMP and activate cAMP-dependent protein kinases but recent evidence implicates another pathway resulting in the phosphorylation of ovarian proteins. This pathway is linked to the hydrolysis of inositol phospholipids, calcium flux and stimulation of calcium dependent protein kinases; one such kinase, protein kinase C, has been implicated in the regulation of a variety of cellular activities in ovarian cells. Importantly, recent evidence has clearly demonstrated the existence of a family of protein kinase C enzymes in hormone-responsive tissues, each displaying different biochemical properties, tissue-distribution and developmental expression.
The specific aims of the proposed research are to identify and characterize protein kinase C isozymes in the bovine corpus luteum. This proposal will focus on fully characterizing ovarian protein kinase C isozymes and documenting their tissue distribution and developmental expression under physiologically relevant conditions in the cow. Measurements of protein kinase activity will be compared with levels of mRNA for specific protein kinase C isozymes. Cultures of bovine small and large luteal cells will provide needed information on the hormonal regulation of protein kinase C isozymes under defined conditions. These studies are expected to improve our knowledge of the mechanism of action of LH and other hormones which control the development and function of the corpus luteum. Understanding these regulatory mechanisms may lead to improved methods of fertility control.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD022248-05A2
Application #
3321733
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1986-08-01
Project End
1996-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Kansas
Department
Type
Schools of Medicine
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160
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Keel, B A; Hildebrandt, J M; May, J V et al. (1995) Effects of epidermal growth factor on the tyrosine phosphorylation of mitogen-activated protein kinases in monolayer cultures of porcine granulosa cells. Endocrinology 136:1197-204
Chakravorty, A; Joslyn, M I; Davis, J S (1993) Characterization of insulin and insulin-like growth factor-I actions in the bovine luteal cell: regulation of receptor tyrosine kinase activity, phosphatidylinositol-3-kinase, and deoxyribonucleic acid synthesis. Endocrinology 133:1331-40
Gangrade, B K; Gotcher, E D; Davis, J S et al. (1993) The secretion of transforming growth factor-beta by bovine luteal cells in vitro. Mol Cell Endocrinol 93:117-23
Davis, J S (1992) Modulation of luteinizing hormone-stimulated inositol phosphate accumulation by phorbol esters in bovine luteal cells. Endocrinology 131:749-57
Duncan, R A; Davis, J S (1991) Prostaglandin F2 alpha stimulates inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate formation in bovine luteal cells. Endocrinology 128:1519-26
Alila, H W; Davis, J S; Dowd, J P et al. (1990) Differential effects of calcium on progesterone production in small and large bovine luteal cells. J Steroid Biochem 36:687-93
Ganguly, A; Chiou, S; West, L A et al. (1989) Atrial natriuretic factor inhibits angiotensin-induced aldosterone secretion: not through cGMP or interference with phospholipase C. Biochem Biophys Res Commun 159:148-54
Davis, J S; Tedesco, T A; West, L A et al. (1989) Effects of human chorionic gonadotropin, prostaglandin F2 alpha and protein kinase C activators on the cyclic AMP and inositol phosphate second messenger systems in cultured human granulosa-luteal cells. Mol Cell Endocrinol 65:187-93
Davis, J S; Alila, H W; West, L A et al. (1989) Second messenger systems and progesterone secretion in the small cells of the bovine corpus luteum: effects of gonadotropins and prostaglandin F2a. J Steroid Biochem 32:643-9

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