Effect of pulsatile @entity12550 administration to the growth-restricted fetal sheep on XXXX gene expression in fetal and placental tissues.

@entity70843 @entity43872 @entity12550 @entity70844 @entity25121 @entity1592 @entity9418 @entity701 @entity10759
We have previously reported (Bauer MK, Breier BH, Bloomfield FH, Jensen EC, Gluckman PD, and Harding JE. J Endocrinol 177: 83-92, 2003) that a chronic pulsatile infusion of @entity12550 ( @entity12550 ) to @entity1592 ( @entity1592 ) ovine fetuses increased fetal circulating @entity9418 levels without increasing fetal growth. We hypothesized a @entity701 -induced upregulation of fetal hepatic @entity43872 ( @entity43872 ) mRNA levels, secondary increases in @entity9418 mRNA levels, and circulating @entity9418 levels, but a downregulation of the type I IGF receptor (IGF-IR) as an explanation. We, therefore, measured mRNA levels of genes of the @entity10759 by real-time RT-PCR in fetal and placental tissues of fetuses with @entity1592 (induced by uteroplacental embolization from 110- to 116-days gestation) that received either a pulsatile infusion of @entity12550 (total dose 3.5 mg/day) or vehicle from 117-126 days and in control fetuses (n = 5 per group). Tissues were collected at 127 days (term, 145 days). Fetal @entity701 concentrations were significantly increased in @entity1592 fetuses. However, in liver, @entity43872 , but not @entity9418 or IGF-IR, mRNA levels were decreased in both @entity1592 groups. In contrast, in placenta, @entity43872 , @entity9418 , and IGF-IR expression were increased in @entity1592 vehicle-infused fetuses. @entity12550 infusion further increased placental @entity43872 and IGF-IR, but abolished the increase in @entity9418 mRNA levels. @entity12550 infusion reduced @entity9418 expression in muscle and increased @entity12550 -R but decreased IGF-IR expression in kidney. @entity1592 increased hepatic @entity25121 and placental @entity70843 mRNA levels with no further effect of @entity12550 infusion. In conclusion, the modest increases in circulating @entity701 concentrations in @entity1592 fetuses did not increase hepatic @entity43872 mRNA expression and, therefore, do not explain the increased circulating @entity9418 levels that we found with @entity12550 infusion, which are likely due to reduced clearance rather than increased production. We demonstrate tissue-specific regulation of the @entity10759 in @entity1592 fetuses and a discontinuity between @entity43872 and @entity9418 gene expression in @entity12550 -infused fetuses that is not explained by alterations in phosphorylated @entity70844 .
