About two thirds of all terrestrial vertebrate species reproduce by oviposition, while the rest of the vertebrates (with few exceptions) by parturition. Prostaglandins (PGs) are among the key components of the mechanism regulating both oviposition and parturition.
The specific aims of this application are a) to test the hypothesis that uterine production of PGs in the domestic hen (Gallus domesticus) is triggered by an oviposition inducing factor (OPIF) of ovarian origin which causes a rapid breakdown of phosphatidylinositol (PI) to phosphatidate (PA), followed by a Ca-dependent activation of phospholipase A2 and the liberation of arachidonic acid resulting in PG-synthesis; b) to examine the regulation of PG receptors in avian and mammalian (rat) uterus in relation to impending oviposition and parturition and c) to define the effects of PGs on the phosphorylation of myometrial cell membrane proteins as well as myosin as possible steps in the contractile action of these powerful biologic substances. Chromatographic (gel-filtration and HPLC) and radioimmunologic methods will be combined with bioassay to isolate and identify the putative OPIF. The proposed effects of OPIF and other agonists will be investigated by following the fate of phospholipids in uterine preparations (prelabeled with [32P] orthophosphate or [3H]arachidonic acid) by means of thin layer radiochromatography and high performance liquid chromatography (HPLC). PG-binding will be studied in myometrial cell membranes prepared by differential and gradient centrifugation of specimens obtained at different times prior to oviposition or parturition. In addition, the effects of steroid hormones on PG-receptors will be examined in vivo and in myometrial slices cultured in vitro. Phosphorylation of uterine proteins will be assessed by determining the incorporation of [32P] or Gamma-32ATP into proteins in the presence of PGs and other agonists. One and two dimensional SDS gel ectophoresis will be applied for the separations of proteins with appropriate molecular markers to estimate the size of the labeled moieties. Successful completion of these studies will provide a unified concept on the role and mechanism of action of PGs in a fundamental process of reproductive biology. Such knowledge will be instrumental for the better understanding of the physiology of labor and pathophysiology of premature labor.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD009763-10
Application #
3311164
Study Section
Reproductive Biology Study Section (REB)
Project Start
1979-04-01
Project End
1989-04-30
Budget Start
1985-05-01
Budget End
1986-04-30
Support Year
10
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Saint Louis University
Department
Type
Schools of Medicine
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63103
Molnar, M; Hertelendy, F (1990) Regulation of intracellular free calcium in human myometrial cells by prostaglandin F2 alpha: comparison with oxytocin. J Clin Endocrinol Metab 71:1243-50
Molnar, M; Hertelendy, F (1990) Ca2+ release and InsP3 production in avian uterine cells: effects of PGF2 alpha and AVT. Am J Physiol 259:E872-80
Molnar, M; Hertelendy, F (1990) PGF2 alpha and PGE2 binding to rat myometrium during gestation, parturition, and postpartum. Am J Physiol 258:E740-7
Houserman, V L; Todd, H; Hertelendy, F (1989) Progesterone treatment in vitro enhances prostaglandin E and forskolin-promoted cyclic AMP production in human endometrial stromal cells. J Reprod Fertil 85:195-202
Asboth, G; Gimes, G; Hertelendy, F et al. (1989) The relation between thromboxane and prostaglandin synthesis in human decidua tissue: a comparison of eicosanoid synthesis in minced tissue with that in a cell-free preparation. Biochim Biophys Acta 1002:101-8
Toth, M; Gimes, G; Hertelendy, F (1987) Triton X-100 promotes the accumulation of phosphatidic acid and inhibits the synthesis of phosphatidylcholine in human decidua and chorion frondosum tissues in vitro. Biochim Biophys Acta 921:417-25
Asem, E K; Todd, H; Hertelendy, F (1987) In vitro effect of prostaglandins on the accumulation of cyclic AMP in the avian oviduct. Gen Comp Endocrinol 66:244-7
Molnar, M; Asem, E K; Hertelendy, F (1987) Differential effects of prostaglandin F2 alpha and of prostaglandins E1 and E2 on cyclic 3',5'-monophosphate production and intracellular calcium mobilization in avian uterine smooth muscle cells. Biol Reprod 36:384-91
Asem, E K; Molnar, M; Hertelendy, F (1987) Luteinizing hormone-induced intracellular calcium mobilization in granulosa cells: comparison with forskolin and 8-bromo-adenosine 3',5'-monophosphate. Endocrinology 120:853-9
Toth, M; Hertelendy, F (1987) Differential effect of progesterone on the labeling of phosphatidylinositol with [3H]inositol and [32P]phosphate in the uterus of the estrogen-treated ovariectomized rat. J Steroid Biochem 28:629-35

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