REGULATION OF EICOSANOID RECEPTORS IN MYOMETRIUM

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Preterm labor is the largest cause of perinatal morbidity and mortality and is directly responsible for 75% of the 36,000 infant deaths per annum in the USA. Eicosanoids (Prostaglandins) are potent mediators of myometrial contractility and are involved in the onset and maintenance of labor. Several eicosanoid receptors have been cloned and sequenced offering opportunities to study their expression and regulation in myometrium throughout gestation and at labor. Myometrial contractility is hormonally regulated by the sex steroids estrogen and progesterone which may alter the sensitivity of myometrium to prostaglandins, i.e., by perhaps altering receptor expression. The objectives of this proposal are to: (1) identify the eicosanoid receptors present in myometrium (2) determine their cellular localization (3) study the ontogeny of expression through gestation and with the onset of labor and (4) examine the hormonal regulation of expression. Studies will primarily use the pregnant rat and will employ several models of hormonal manipulation that either induce preterm labor or prevent the onset of labor in this species. Parallel studies will be performed in pregnant human myometrium obtained from four groups of patients, at term either in or not in labor or preterm either in or not in labor. To achieve these objectives, the proposed experiments will utilize reverse transcription-polymerase chain reaction, northern blotting and in situ hybridization. These studies will provide novel data on the expression of eicosanoid receptors in relation to the onset of myometrial contractility. Ultimately, this knowledge may be beneficial in providing new uterine selective methods of tocolysis.