The present research proposal evolved from a clinical study in which we found that LHRH was luteolytic when administered during the luteal phase of the cycle. In the same study, it was found that pharmacologic doses of gonadotropin did not cause apparent down-regulation of luteal LH receptors as it did the rat. More recently, we showed that LHRH and LHRH analogs showed acute and direct antigonadotropic activity in rat luteal cells. The objective of the present proposal is first to determine if LHRH and LHRH analogs show direct antigonadotropic activity in human ovarian cells in vitro and, if so, evaluate the cellular basis of this activity; second, to assess if LHRH may play a physiological (and/or pathological) role as a direct modulator of gonadotropin action in the ovary; and third, examine whether other antigonadotropic proteins (peptides) serving such functions may be present in ovarian and uterine tissues and fluids. This research will be based on cell dispersion and short- and long-term culture techniques, radioimmunoassay of gonadal steroids and LHRH, receptor binding studies for LHRH and LH, and protein-peptide extraction and assay techniques. This information may lead to an understanding of the mechanism of the luteolytic action of LHRH in the human female and possibly identify other antigonadotropins of ovarian origin of which LHRH is a pharmacologic agonist.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD015403-07
Application #
3313063
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1981-04-01
Project End
1989-06-30
Budget Start
1987-04-01
Budget End
1988-06-30
Support Year
7
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Margolin, Y; Aten, R F; Behrman, H R (1992) Mechanisms for the antigonadotropic action of the ovarian gonadotropin-releasing hormone-binding inhibitor protein/histone H2A on ovarian cells. Biol Reprod 46:1021-6
Ireland, J J; Milvae, R A; Martin, T L et al. (1990) Effect of histone H2A on progesterone production by bovine luteal cells. Biol Reprod 43:1058-63
Behrman, H R; Aten, R F; Margolin, Y (1989) Gonadotropin-releasing hormone binding inhibitors in the ovary. Can J Physiol Pharmacol 67:954-6
Aten, R F; Behrman, H R (1989) A gonadotropin-releasing hormone-binding inhibitor from bovine ovaries. Purification and identification as histone H2A. J Biol Chem 264:11065-71
Aten, R F; Behrman, H R (1989) Antigonadotropic effects of the bovine ovarian gonadotropin-releasing hormone-binding inhibitor/histone H2A in rat luteal and granulosal cells. J Biol Chem 264:11072-5
Behrman, H R; Aten, R F; Ireland, J J et al. (1989) Characteristics of an antigonadotrophic GnRH-like protein in the ovaries of diverse mammals. J Reprod Fertil Suppl 37:189-94
Soodak, L K; Musicki, B; Behrman, H R (1988) Selective amplification of luteinizing hormone by adenosine in rat luteal cells. Endocrinology 122:847-54
Behrman, H R (1988) The history of hormone assays. Prog Clin Biol Res 285:1-14
Behrman, H R; Preston, S L; Pellicer, A et al. (1988) Oocyte maturation is regulated by modulation of the action of FSH in cumulus cells. Prog Clin Biol Res 267:115-35
Ireland, J J; Aten, R F; Behrman, H R (1988) GnRH-like proteins in cows: concentrations during corpora lutea development and selective localization in granulosal cells. Biol Reprod 38:544-50

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