The following proposal outlines our interest in the role of intercellular communication in the control of reproductive function in mammals. Evidence is provide for the regulation of ovarian and uterine cell surface structures termed gap junctions which are involved in the direct exchange of a variety of small regulatory and informational molecules between cells in contact. The anatomical basis for the establishment of coordinated uterine smooth muscle activity during labor is due to the appearance of myometrial cell gap junctions which facilitates electrical coupling and thereby a single electrical syncytium during parturition. The studies outlined in this proposal are designed to provide a unique experimental approach to the analysis of the mechanisms regulating intercellular communication in the mammalian uterus. The objective of the research are: (a) To study the action of estrogen and progesterone on the formation of myometrial gap junctions in vitro and compare the permeability properties of myometrial gap junctions with those of vascular smooth muscle cells: (b) to test the hypothesis that the permeability of gap junctions in myometrium can be modulated by cAMP and the inositol phospholipid signal transduction pathways; (c) to develop myometrial cell-granulosa co-culture systems in order to analyze differences in the regulatory mechanisms affecting gap junction channel permeability: (d) to test the hypothesis that electron dense deposits associated with gap junction membrane following receptor mediated activation off the cAMP pathway represents Ca++ trapped by adenylyl cyclase derived pyrophosphate anions. As prematurity is associated with over 60% of all infant deaths, reduction of this hazard requires research on the factors that maintain pregnancy and initiate labor. The results of these studies will lead to a better understanding of uterine myometrial contractility during parturition and hopefully, to the development of effective tocolytic agents.
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| Dookwah, H D; Barhoumi, R; Narasimhan, T R et al. (1992) Gap junctions in myometrial cell cultures: evidence for modulation by cyclic adenosine 3':5'-monophosphate. Biol Reprod 47:397-407 |
| Stein, L S; Boonstra, J; Burghardt, R C (1992) Reduced cell-cell communication between mitotic and nonmitotic coupled cells. Exp Cell Res 198:1-7 |
