Control of growth hormone receptor and insulin-like growth factor-I expression by cortisol in ovine fetal skeletal muscle

Insulin-like growth factor (IGF)-I has an important role in myogenesis but its developmental regulation in skeletal muscle before birth remains unknown. In other tissues, cortisol modulates IGF gene expression and is responsible for many of the prepartum maturational changes essential for neonatal survival. Hence, using RNase protection assays and ovine riboprobes, expression of the IGF-I and growth hormone receptor (GHR) genes was examined in ovine skeletal muscle during late gestation and after experimental manipulation of fetal plasma cortisol levels by fetal adrenalectomy and exogenous cortisol infusion. Muscle IGF-I, but not GHR, mRNA abundance decreased with increasing gestational age in parallel with the prepartum rise in plasma cortisol. Abolition of this cortisol surge by fetal adrenalectomy prevented the prepartum fall in muscle IGF-I mRNA abundance. Conversely, raising cortisol levels by exogenous infusion earlier in gestation prematurely lowered muscle IGF-I mRNA abundance but had no effect on GHR mRNA. When all data were combined, plasma cortisol and muscle IGF-I mRNA abundance were inversely correlated in individual fetuses. Cortisol is, therefore, a developmental regulator of IGF-I gene expression and is responsible for suppressing expression of this gene in ovine skeletal muscle near term. These observations have important implications for muscle development both before and after birth, particularly during conditions which alter intrauterine cortisol exposure.