The overall objective of this research is to investigate the endocrine regulation of cell differentiation and of progesterone synthesis in the corpus luteum of the rat and rabbit. Specifically, the physiological role of the theca lutein cell and the role of estrogen and of LH in the differentiation of the granulosa lutein cell will be emphasized. Two basic approaches, recently developed in this laboratory, will be used. First, transplants of luteinizing granulosa cells or of luteinizing whole follicles will be made into hypophysectomized Fischer 344 rats and in rabbits. Second, granulosa lutein cells from rabbits will be studied in monolayer cultures. The following hypotheses will be tested: 1) androgen (or its aromatized derivative) and prolactin are necessary for increased steroidogenic capacity and further differentiation of rat granulosa lutein cells in the second week after ovulation; 2) an important role of the theca lutein cell is its participation in luteal estrogen synthesis, which is stimulated by LH (rat); 3) the small steroidogenic cell population in rat and rabbit corpora lutea is derived from thecal cells of the follicle; 4) the role of LH in the rabbit corpus luteum is to stimulate the recruitment or differentiation of small luteal cells, suspected to be of thecal origin; 5) differentiation and progesterone synthesis by granulosa lutein cells in culture can be stimulated either by LH or by estradiol; the steroidogenic effect of estradiol is mediated by 3'5' - cyclic AMP (rabbit). These studies are expected to lead to new understanding of the interactions between cell populations in the corpus luteum and of the hormones that govern the normal function and regression of the corpus luteum.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD007127-17
Application #
3310637
Study Section
Reproductive Biology Study Section (REB)
Project Start
1978-03-01
Project End
1990-12-31
Budget Start
1988-07-01
Budget End
1990-12-31
Support Year
17
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Seiner, S J; Schramm, W; Keyes, P L (1992) Effect of treatment with methylprednisolone on duration of pseudopregnancy and on macrophages and T lymphocytes in rabbit corpora lutea. J Reprod Fertil 96:347-53
Hunzicker-Dunn, M; Chen, A; Jackiw, V et al. (1991) Luteal enzymes of the luteinizing hormone and beta-adrenergic signal transduction pathways in hypophysectomized rabbits do not require pituitary hormone support. Biol Reprod 44:609-19
Constantino, C X; Keyes, P L; Kostyo, J L (1991) Insulin-like growth factor-I stimulates steroidogenesis in rabbit luteal cells. Endocrinology 128:1702-8
Wiltbank, M C; Gallagher, K P; Christensen, A K et al. (1990) Physiological and immunocytochemical evidence for a new concept of blood flow regulation in the corpus luteum. Biol Reprod 42:139-49
Keyes, P L; Kostyo, J L; Hales, D B et al. (1990) The biosynthesis of cholesterol side-chain cleavage cytochrome P-450 in the rabbit corpus luteum depends upon estrogen. Endocrinology 127:1186-93
Bagavandoss, P; Wiggins, R C; Kunkel, S L et al. (1990) Tumor necrosis factor production and accumulation of inflammatory cells in the corpus luteum of pseudopregnancy and pregnancy in rabbits. Biol Reprod 42:367-76
Wiltbank, M C; Gallagher, K P; Dysko, R C et al. (1989) Regulation of blood flow to the rabbit corpus luteum: effects of estradiol and human chorionic gonadotropin. Endocrinology 124:605-11
Bagavandoss, P; Kunkel, S L; Wiggins, R C et al. (1988) Tumor necrosis factor-a (TNF-a) production and localization of macrophages and T lymphocytes in the rabbit corpus luteum. Endocrinology 122:1185-7
Wiltbank, M C; Dysko, R C; Gallagher, K P et al. (1988) Relationship between blood flow and steroidogenesis in the rabbit corpus luteum. J Reprod Fertil 84:513-20
Keyes, P L; Wiltbank, M C (1988) Endocrine regulation of the corpus luteum. Annu Rev Physiol 50:465-82

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