The major objective of the proposed research is to gain a better understanding of the hormonal regulation of the rat corpus luteum during pregnancy and pseudopregnancy. Particular attention will be given to the local action of estrogen within the corpus luteum and to the role of the thecal lutein cell in the normal activity of the corpus luteum. The importance of the thecal lutein cell will be evaluated by investigating the functional capabilities (progesterone and 20Alpha-dihydroprogesterone synthesis, estradiol synthesis, aromatase activity, prolactin and LH receptor) of luteal tissue formed in the absenceof thecal lutein cells. This will be accomplished by the method of granulosa cell homotransplantation, recently developed in this laboratory. The concept that estrogen, formed in the corpus luteum, mediates certain actions of LH will be examined further by: a) determining if LH can stimulate estrogen synthesis in the corpus luteum; b) role of estrogen in mediating LH action to maintain progesterone synthesis and in predisposing luteal regression; c) role of estrogen in maintaining optimal luteal blood flow and in maintaining the normal morphology and ultrastructure of the luteal vascular system. For some of these studies, hypophysectomized rates with homotransplanted pituitary will be used. To determine direct effects of hormones on the corpus luteum, we will use rats with ectopic orpora lutea located beneath the kidney capsule. Blood flow in the corpus luteum will be determined by the reference sample radioactive microsphere method. Finally, certain aspects of luteal regression will be investigated by determining, a) if regressing luteal cells produce substances inimical to progesterone synthesis using transplants of mixed populations of regressing and non-regressing luteal cells; and, b) if the luteolytic effect of LH is via loss of luteal estrogen synthesis.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD007127-14
Application #
3310635
Study Section
Reproductive Biology Study Section (REB)
Project Start
1978-03-01
Project End
1986-06-30
Budget Start
1985-03-01
Budget End
1986-06-30
Support Year
14
Fiscal Year
1985
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

Showing the most recent 10 out of 14 publications