Pregnancy

Insulin-Like Growth Factors and Their Binding Proteins Define Specific Phases of Myometrial Differentiation During Pregnancy

Abstract
While the IGF system is know to regulate uterine function during the estrous cycle there is limited data on its role in myometrial growth and development during pregnancy. To address this issue we defined the expression of the Igf hormones (1 and 2), their binding proteins (Igfbp 1-6) and Igf1r receptor genes in pregnant, laboring and post-partum rat myometrium by real-time PCR. IGF family genes were differentially expressed throughout gestation. Igf1 and Igfbp1 mRNA levels were up-regulated during proliferative phase (day 6-12) of rat gestation. Igfbp3 gene expression was also elevated in proliferating smooth muscle cells (SMCs) and highest at the time of transition between proliferative and synthetic phases (day 12-15). Igfbp6 gene expression profile paralleled plasma progesterone (P4) concentrations, peaking during the synthetic phase (day 17-19) and decreasing thereafter. Administration of P4 at late pregnancy (starting from day 20) to maintain elevated plasma P4 concentrations blocked the onset of labor and prevented the fall in Igfbp6 mRNA levels. In contrast, the treatment of pregnant rats with the P4 receptor antagonist RU486 on day 19 induced preterm labor and the premature decrease of Igfbp6 gene expression. Igfbp2 gene expression was transiently up-regulated during the contractile phase of gestation (day 21-23) solely in the gravid horn of unilaterally pregnant rats, but was not affected in P4- or RU486-treated animals, supporting a role for mechanical stretch imposed by the growing fetuses. Igfbp5 gene was induced during postpartum involution. Our results suggest the importance of the IGF system in phenotypic and functional changes of myometrial SMCs throughout gestation in preparation for labor.

Key words: Pregnancy • Insulin-like growth factor receptor • Parturition • Progesterone • Uterus

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