Abstract

Our long term goals are to understand the interaction between OT and PGs and their importance in the initiation of labor. The principal goal of this proposal is to determine the relationship between the occupancy of OT binding sites in decidua, endometrium and amnion and the production of PGs.
The specific aims are to: 1. Study OT binding sites in decidua, endometrium and amnion with respect to affinity, concentration, ligand specificity, and metal ion requirements. 2. Show the relationship between OT binding and PG release in these tissues, with respect to OT agonists and antagonists. 3. Study the relationship between changes in OT sensitivity of PG release and changes in the concentration of OT receptors. We will study decidua from guinea pigs and rabbits at different stages of pregnancy and guinea pig endometrium during the estrous cycle. 4. Study effects of estrogen and progesterone, administered both in vivo and in vitro, on OT receptor concentrations in guinea pig and rabbit endometrium and cultured human amnion cells. We hope to establish whether steroid-induced changes in receptor concentration are related to changes in the sensitivity of the release of PGs. 5. Establish the validity of using an iodinated OT antagonist, previously shown to bind specifically to OT receptors in. the myometrium, mammary gland and regions of the brain, as a probe for OT receptors in the endometrium, decidua, and amnion. The use of iodinated antagonist would greatly reduce the amount-of tissue needed for subsequent studies. 6. Study physicochemical properties of OT receptors in the endometrium/decidua and possibly amnion. These studies include determination of the functional molecular mass by radiation inactivation studies, the size of the binding unit by photoaffinity cross-linking and solubilization studies, as carried out by us previously with OT receptors in the rat mammary gland. These studies will form the basis for later work elucidating the mechanisms by which OT stimulates PG production.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD026168-03
Application #
3327536
Study Section
Special Emphasis Panel (SRC (17))
Project Start
1989-08-01
Project End
1994-04-30
Budget Start
1991-05-01
Budget End
1992-04-30
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
University of Toledo
Department
Type
Schools of Medicine
DUNS #
807418939
City
Toledo
State
OH
Country
United States
Zip Code
43614

  Publications

Copland, John A; Zlatnik, Marya G; Ives, Kirk L et al. (2002) Oxytocin receptor regulation and action in a human granulosa-lutein cell line. Biol Reprod 66:1230-6
Jeng, Y J; Liebenthal, D; Strakova, Z et al. (2000) Complementary mechanisms of enhanced oxytocin-stimulated prostaglandin E2 synthesis in rabbit amnion at the end of gestation. Endocrinology 141:4136-45
Soloff, M S; Jeng, Y J; Copland, J A et al. (2000) Signal pathways mediating oxytocin stimulation of prostaglandin synthesis in select target cells. Exp Physiol 85 Spec No:51S-58S
Hoare, S; Copland, J A; Strakova, Z et al. (1999) The proximal portion of the COOH terminus of the oxytocin receptor is required for coupling to g(q), but not g(i). Independent mechanisms for elevating intracellular calcium concentrations from intracellular stores. J Biol Chem 274:28682-9
Jeng, Y J; Lolait, S J; Soloff, M S (1998) Induction of oxytocin receptor gene expression in rabbit amnion cells. Endocrinology 139:3449-55
Strakova, Z; Copland, J A; Lolait, S J et al. (1998) ERK2 mediates oxytocin-stimulated PGE2 synthesis. Am J Physiol 274:E634-41
Strakova, Z; Soloff, M S (1997) Coupling of oxytocin receptor to G proteins in rat myometrium during labor: Gi receptor interaction. Am J Physiol 272:E870-6
Jeng, Y J; Hinko, A; Soloff, M S (1995) Effectors of cyclic adenosine 5'-monophosphate up-regulating-oxytocin receptors in rabbit amnion cells: isoproterenol, parathyroid hormone-related protein, and potentiation by cortisol. Biol Reprod 53:1051-6
Czaja, M; Kruszynski, M; Hinko, A et al. (1994) Arginine vasopressin antagonism of oxytocin-stimulated PGE2 release from rabbit amnion cells and the activities of thioanalogs of oxytocin and arginine vasopressin. Pol J Pharmacol 46:429-37
Hinko, A; Soloff, M S (1993) Up-regulation of oxytocin receptors in rabbit amnion by adenosine 3',5'-monophosphate. Endocrinology 132:126-32

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