The prostaglandins belong to a large group of naturally occurring paracrine mediators of physiologic responses. One of the prostaglandins, prostaglandin F 2alpha (PGF 2alpha), is important in responses such as: myometrial contraction, bronchoconstriction, luteolysis, movement of the egg/zygote through the oviduct, and growth of endometrial and osteoblastic cells. PGF 2alpha may also be one of the paracrine factors through which estrogen elicits its effects on the uterus, ovary and breast. As such, abnormalities in the normal functioning of PGF 2alpha, or of its naturally occurring antagonist prostaglandin E, could be responsible for altered states of uterine contraction, bronchoconstriction, fertility, or growth of uterus and bone. I believe that a better biochemical characterization of the PGF 2alpha receptor and elucidation of the control of expression of the gene that codes for this receptor would facilitate understanding of how this prostaglandin achieves those normal physiologic functions for which it is responsible. Similarly, it may help us understand the role of PGF 2alpha in diseases such as dysmenorrhea (PMS), endometrial hyperplasia, ovarian cancer and infertility, among others. Therefore, the specific aims to be addressed in this grant are the continued development of the anti-PGF 2alpha receptor antibody tool and its use in immunohistochemical and immunoprecipitation studies and in isolating the cDNA for the PGF 2alpha receptor. This PGF 2alpha receptor CDNA will then be sequenced providing the amino acid sequence of the receptor as well as a hint of its structural and enzymatic properties. The PGF 2alpha receptor cDNA will also be used as a tool to measure PGF 2alpha receptor mRNA levels in normal and hormonal stimulated tissues.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD025961-05
Application #
2199781
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1989-08-01
Project End
1995-06-30
Budget Start
1993-07-01
Budget End
1995-06-30
Support Year
5
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Pathology
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
Orlicky, D J (1996) Negative regulatory activity of a prostaglandin F2 alpha receptor associated protein (FPRP). Prostaglandins Leukot Essent Fatty Acids 54:247-59
Orlicky, D J; Berry, R; Sikela, J M (1996) Human chromosome 1 localization of the gene for a prostaglandin F2alpha receptor negative regulatory protein. Hum Genet 97:655-8
Orlicky, D J; Nordeen, S K (1996) Cloning, sequencing and proposed structure for a prostaglandin F2 alpha receptor regulatory protein. Prostaglandins Leukot Essent Fatty Acids 55:261-8
Orlicky, D J; Williams-Skipp, C (1993) Immunohistochemical localization of PGF2 alpha receptor in the rat oviduct. Prostaglandins Leukot Essent Fatty Acids 48:185-92
Orlicky, D J; Fisher, L; Dunscomb, N et al. (1992) Immunohistochemical localization of PGF2 alpha receptor in the rat ovary. Prostaglandins Leukot Essent Fatty Acids 46:223-9
Golinski, M; Heine, M; Orlicky, D J et al. (1992) Prostaglandin photoaffinity probes: synthesis and binding affinity of C-18 substituted PGF2 alpha prostanoids bearing a perfluorinated aryl azide. Eicosanoids 5:87-97
Orlicky, D J; Williams-Skipp, C (1992) Immunohistochemical localization of PGF2 alpha receptor in the mouse testis. Prostaglandins Leukot Essent Fatty Acids 47:247-52
Golinski, M; Heine, M; Orlicky, D J et al. (1992) Prostaglandin photoaffinity probes: synthesis and binding affinity of aryl azide-substituted C-1 esters of prostaglandin F2 alpha. Eicosanoids 5:99-107
Kawada, K; Pralong, E; Vesin, M F et al. (1991) Prostaglandin photoaffinity probes: synthesis and binding affinity of an azide-substituted 17-phenyl PGE2 prostaglandin. Eicosanoids 4:57-60
Platz, M; Admasu, A S; Kwiatkowski, S et al. (1991) Photolysis of 3-aryl-3-(trifluoromethyl)diazirines: a caveat regarding their use in photoaffinity probes. Bioconjug Chem 2:337-41

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