THE ONTOGENY OF HEPATIC GROWTH-HORMONE RECEPTOR AND INSULIN-LIKE GROWTH-FACTOR-I GENE-EXPRESSION IN THE SHEEP FETUS DURING LATE-GESTATION -DEVELOPMENTAL REGULATION BY CORTISOL

The effects of cortisol on hepatic GH receptor and insulin-like growth factor-I (IGF-I) gene expression were investigated in sheep fetuses d uring late gestation and after experimental manipulation of plasma cor tisol levels by fetal adrenalectomy and exogenous infusion of cortisol . Hepatic GH receptor and IGF-I messenger RNA (mRNA) levels increased with increasing gestational age in parallel with the normal rise in fe tal cortisol levels toward term (145 +/- 2 days). These increases in m RNA abundance toward term were prevented when the prepartum cortisol s urge was abolished by fetal adrenalectomy and were stimulated prematur ely in fetuses younger than 130 days by exogenous infusion of cortisol . Both the class 1 and class 2 transcripts of the IGF-I gene were incr eased when cortisol levels were elevated either endogenously or exogen ously. However, there were no significant changes in fetal plasma IGF- I levels either with increasing gestational age or in response to expe rimental manipulation of the fetal cortisol level. When the data from all the fetuses were combined irrespective of treatment or gestational age, there were significant positive correlations between the log pla sma cortisol concentration in utero and the abundance of GH receptor a nd IGF-I mRNA in the fetal liver. There was also a significant inverse relationship between log plasma cortisol and the ratio of class 1 to class 2 transcript abundance in the fetal liver. These findings show t hat cortisol is a physiological regulator of hepatic GH receptor and I GF-I gene expression in fetal sheep during late gestation and indicate that it preferentially increases the class 2 transcript of the IGF-I gene. The prepartum cortisol surge therefore appears to have an import ant maturational role in initiating the perinatal switch from the feta l to adult modes of somatotrophic regulation.