The prostaglandins belong to a large group of naturally occurring paracrine mediators of physiologic responses. Two of the prostaglandins, prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E (either E1 or E2, here grouped as PGE), apparently act in an agonist/antagonist fashion. For example, PGF2 alpha is a paracrine growth factor of both endometrium and breast, and its stimulation of proliferation can be antagonized by PGE. PGF2 alpha may be one of the local paracrine factors through which estrogen stimulates growth of the uterus and breast. As such, defects in this naturally occurring prostaglandin check and balance of growth may be responsible for abnormal growth states such as hyperplasia and cancer. We believe that precise identification, purification, biochemical characterization and histochemical localization of these receptors is a prerequisite for understanding exactly which cells in a tissue respond o these prostaglandins, and understanding how these prostaglandins achieve the normal physiologic hemostasis observed in the tissues in which they function. We should like to point out that this approach has been quite fruitful in understanding the roles of estrogen and progesterone in breast and uterine tissue. Therefore, the specific aims o be addressed in this grant are the molecular identification of these prostaglandin receptors using novel photoaffinity probes of both PGF2 and PGE, isolation of sufficient quantities of these receptors for chemical characterization and for use as antigens, and preparation and characterization of antibodies against these receptors. It is our contention that both the naturally occurring agonist and antagonist should be examined since it is the relative balance of these two factors operating in unison which produce a physiologic response. Results generated from these studies will have a bearing on all tissues possessing either PGF2 alpha or PGE receptors and on the general phenomena of paracrine control of physiologic unction. In particular, the histochemical localization of these receptors may have diagnostic value in breast and endometrial hyperplasia (cancer?), as well as in dysmenorrhea.
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