The ovary secretes both steroid hormones and a spectrum of protein hormones that are of great importance to the control of reproductive function. However, little is presently known of the cellular and molecular pathways that regulate release of ovarian protein hormones. In these proposed studies, a more complete understanding of one such hormone, the protein hormone relaxin, will be attempted by characterizing the secretagogues and intracellular signalling pathways that subserve secretory function, together with an analysis of structure-function relationships. These objectives will be met by use of a reverse hemolytic plaque assay. This assay is based on antibody-directed, complement- mediated lysis of erythrocytes adjacent to hormone secretors, thus enabling the microscopic visualization of hormone release from individual luteal cells in culture. The primary objectives of the proposed studies are: (a) to evaluate the relative importance of, and differential response to, stimulatory (prostaglandins) and inhibitory (LH, auto-suppression) secretagogues for relaxin release; (b) to characterize the influence, interactions and relative importance of, and differential response to, second messenger pathways such as cyclic nucleotides, calcium mobilization, protein kinase C activation and arachidonic acid metabolites, and to determine if luteal cells function as excitable cells; and (c) to determine the secretory characteristics of luteal cells that contain relaxin but do not release relaxin (""""""""silent"""""""" cells""""""""). To accomplish these goals, the secretory characteristics of single hormone-secretors will be monitored, in combination (where appropriate) with immunocytochemical techniques. It is anticipated that meaningful information will be derived concerning the identity, importance and interactions of cellular and molecular mechanisms that subserve ovarian hormone release. Moreover, new insights into the enigma of non-releasing secretory cells will be gained. This knowledge can eventually be used not only to identify the causes of (and developing treatments for) ovarian pathologies, but also to identify new strategies for regulating human ovarian function.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD022786-01A2
Application #
3322650
Study Section
Reproductive Biology Study Section (REB)
Project Start
1989-04-01
Project End
1992-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Iowa State University
Department
Type
Schools of Veterinary Medicine
DUNS #
City
Ames
State
IA
Country
United States
Zip Code
50011
Takayama, Sachiko; Hostick, Ute; Haendel, Melissa et al. (2008) An F-domain introduced by alternative splicing regulates activity of the zebrafish thyroid hormone receptor alpha. Gen Comp Endocrinol 155:176-89
Taylor, M J; Hehnke, K; Clark, C L (1993) Lipopolysaccharide and a phorbol ester stimulate secretion of tumor necrosis factor-alpha from alveolar macrophages through action on overlapping subsets of cells. J Leukoc Biol 54:384-8
Taylor, M J; Clark, C L (1993) Relaxin secretion by porcine large luteal cells: effect of protein synthesis inhibitors. Proc Soc Exp Biol Med 202:148-52
Taylor, M J; Clark, C L (1992) Transforming growth factor-beta is a potent inhibitor of basal and stimulated relaxin release by porcine luteal cells maintained in monolayer culture. J Endocrinol 135:543-50
Taylor, M J; Clark, C L (1992) Basic fibroblast growth factor inhibits basal and stimulated relaxin secretion by cultured porcine luteal cells: analysis by reverse hemolytic plaque assay. Endocrinology 130:1951-6
Taylor, M J; Clark, C L (1992) Discordant secretion of relaxin by individual porcine large luteal cells: quantitative analysis by a reverse haemolytic plaque assay. J Endocrinol 134:77-83
Taylor, M J; Clark, C L (1992) Evidence that basal secretion of relaxin by individual cultured large luteal cells is influenced by mobilization of intracellular calcium: analysis by a reverse hemolytic plaque assay. Cell Calcium 13:571-80
Taylor, M J; Clark, C L (1990) Effect of antimicrotubule agents on secretion of relaxin by large luteal cells derived from pregnant swine. Endocrinology 126:1790-5
Taylor, M J; Clark, C L (1989) Analysis of relaxin release by cultured porcine luteal cells using a reverse hemolytic plaque assay: effects of arachidonic acid, cyclo- and lipooxygenase blockers, phospholipase A2, and melittin. Endocrinology 125:1389-97