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The expression of transforming growth factor ß in pregnant rat myometrium is hormone and stretch dependent

¹ Samuel Lunenfeld Research Institute at Mount Sinai, Mount Sinai Hospital, 600 University Avenue, Suite 870, Toronto, Ontario, Canada M5G 1X5, ² Departments of Physiology and ³ Obstetrics and Gynecology, University of Toronto, Toronto, Canada M5S 1A1 and ⁴ Toronto General Research Institute, University Health Network, Toronto, Canada M5G 2C4

Correspondence should be addressed to S J Lye; Email: lye{at}mshri.on.ca

From a quiescent state in early pregnancy to a highly contractile state in labor, the myometrium displays tremendous growth and remodeling. We hypothesize that the transforming growth factor ß (TGFß) system is involved in the differentiation of pregnant myometrium throughout gestation and labor. Furthermore, we propose that during pregnancy the mechanical and hormonal stimuli play a role in regulating myometrial TGFßs. The expression of TGFß1-3 mRNAs and proteins was examined by real-time PCR, Western immunoblot, and localized with immunohistochemistry in the rat uterus throughout pregnancy and labor. Tgfß1-3 genes were expressed differentially in pregnant myometrium. Tgfß2 gene was not affected by pregnancy, whereas the Tgfß1 gene showed a threefold increase during the second half of gestation. In contrast, we observed a dramatic bimodal change in Tgfß3 gene expression throughout pregnancy. Tgfß3 mRNA levels first transiently increased at mid-gestation (11-fold on day 14) and later at term (45-fold at labor, day 23). Protein expression levels paralleled the changes in mRNA. Treatment of pregnant rats with the progesterone (P4) receptor antagonist RU486 induced premature labor on day 19 and increased Tgfß3 mRNA, whereas artificial maintenance of elevated P4 levels at late gestation (days 20–23) caused a significant decrease in the expression of Tgfß3 gene. In addition, Tgfß3 was up-regulated specifically in the gravid horn of unilaterally pregnant rats subjected to a passive biological stretch imposed by the growing fetuses, but not in the empty horn. Collectively, these data indicate that the TGFß family contributes in the regulation of myometrial activation at term integrating mechanical and endocrine signals for successful labor contraction.

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