REGULATION OF STEROID HYDROXYLASE GENE-EXPRESSION IN THE OVINE FETAL ADRENAL-GLAND AT 0.4 GESTATION

This study was designed to test the hypothesis that ACTH from the feta l pituitary is a major regulator of adrenocortical steroid . hydroxyla se gene expression in the ovine fetus at 0.4 (60-70 days) of gestation . Pregnant ewes at 0.4 gestation received intravenous infusions of dex amethasone (0.76 mg/h, n = 13) for 48 h. The rationale for this regime was that some of the infused dexamethasone would cross the placenta a nd act on the fetal pituitary to suppress ACTH release. Control animal s received infusions,of saline (0.38 ml/h, n = 12) for 48 h. At the en d of the infusion period, the animals were killed, umbilical vessel bl ood taken for ACTH and cortisol analyses, and the fetal adrenal glands taken for assessment of P-450(scc), P-450(17 alpha) and P-450(c21) le vels using the techniques of hybridization histochemistry and RNase pr otection assay. Dexamethasone treatment; decreased maternal and fetal concentrations of ACTH to 29 +/- 10 and <20 pg/ml, respectively and co rtisol concentrations to 3.5 +/- 0.6 and 3.2 +/- 0.8 nmol/l respective ly. The adrenal glands from the dexamethasone-treated fetuses exhibite d significantly lower levels of mRNA for P450(scc) (11% of control) an d P-450(17 alpha) (2% of control). These results suggest that ACTH is a major regulator of steroid hydroxylase gene expression and subsequen t cortisol biosynthesis in vivo in the ovine fetus at 0.4 gestation.