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.
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