HORMONAL CONTROL OF C-KINASE AND CORPUS LUTEUM FUNCTION

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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.