INSULIN-LIKE GROWTH FACTOR-II MESSENGER-RIBONUCLEIC-ACID EXPRESSION IN FETAL TISSUES OF THE SHEEP DURING LATE GESTATION - EFFECTS OF CORTISOL

Using RNase protection analysis, insulin-like growth factor-II (IGF-II ) mRNA levels were measured in various tissues from fetal sheep during late gestation (term, 146 +/- 2 days) and after experimental manipula tion of fetal plasma cortisol levels. No gestational trend in IGF-II m RNA levels was observed in the fetal lung, kidney, or skeletal muscle. However, in the fetal liver, there was a marked decline in IGF-II mRN A abundance immediately before term, which closely paralleled the norm al prepartum surge in fetal plasma cortisol. This decrease in hepatic IGF-II mRNA levels toward term was prevented when the cortisol surge w as abolished by fetal adrenalectomy and was stimulated prematurely in fetuses younger than 130 days by exogenous infusion of cortisol. Hepat ic and renal IGF-II mRNA abundances were also reduced when fetal corti sol levels were raised endogenously by maternal fasting in late gestat ion. Muscle IGF-II mRNA levels were reduced by fetal cortisol infusion , but not by maternal fasting, and were higher in adrenalectomized tha n in intact fetuses in late gestation. No change in IGF-II mRNA levels were observed in the fetal lung in response to altering the fetal cor tisol level either exogenously or endogenously. When the data from all fetuses were combined regardless of treatment or gestational age, the re was a significant inverse correlation between the plasma cortisol l evel in utero and IGF-II mRNA abundance in the fetal liver (P < 0.001) , but not in any of the other fetal tissues studied. These findings sh ow that cortisol suppresses IGF-II gene expression in the liver of the sheep fetus and indicate that the developmental change in hepatic IGF status toward term may be due to the prepartum cortisol surge.