REGULATION OF INSULIN-LIKE GROWTH FACTOR-II GENE-EXPRESSION IN THE OVINE FETAL ADRENAL-GLAND BY ADRENOCORTICOTROPIC HORMONE AND CORTISOL

Maturation and activation of the fetal adrenal gland is crucial to fet al organ maturation and the onset of parturition in sheep. Insulinlike growth factors (IGFs) have been demonstrated to promote fetal adrenal mitogenesis and steroidogenesis in some species. Our previous studies showed that IGF-II mRNA is expressed in the steroidogenic cells of th e fetal sheep adrenal, suggesting that IGF-II may be an important regu lator of fetal adrenal function. However, the regulation of IGF-II gen e expression is poorly understood. In the present study we measured th e changes in IGF-II mRNA level in fetal sheep adrenals during late ges tation in response to ACTH and cortisol. Either saline (0.5 ml/h) or c ortisol(l mg/24 h) was infused for 100 h to fetal sheep beginning on d ay 95 or 96 of pregnancy, or saline (0.5 ml/h), ACTH (0.5 mu g/h), or cortisol (1 mg/h) was infused for 84 h to fetal sheep beginning on day s 120-125 of pregnancy (term = 145 days). Adrenal RNA was subjected to Northern blot analysis with an ovine IGF-II cDNA probe. The relative abundance of total IGF-II mRNA decreased significantly in the ACTH- an d cortisol-treated fetuses. IGF-II mRNA was localized by in situ hybri dization using a S-35-labeled antisense ovine IGF-II cRNA probe, and I GF-II peptide was localized by immunohistochemistry. There were no dif ferences in the cellular distribution patterns of IGF-II mRNA and IGF- II peptide after treatments, but the intensity of the hybridization si gnal for IGF-II mRNA and of immunostaining for IGF-II peptide decrease d in adrenals from fetuses treated with ACTH or cortisol. These result s suggest that ACTH and cortisol decrease IGF-II gene expression in th e ovine fetal adrenal. We speculate that the cortisol surge observed i n the late gestation ovine fetus may be responsible for down-regulatio n of IGF-II gene expression in the fetal adrenal at or just before bir th.