Infusion of N-proopiomelanocortin-(1-77) increases adrenal weight and messenger ribonucleic acid levels of cytochrome P-450 17 alpha-hydroxylase in the sheep fetus during late gestation

the sheep there is a rapid increase in fetal adrenal growth and steroidogen esis during the last 10-15 days gestation (term = 147 +/- 3 days gestation) . In the rat, peptides derived from the N-terminal region of POMC play a ro le in compensatory adrenal growth and in potentiation of ACTH-induced stero idogenesis. We therefore investigated the effects of infusion of bovine N-P OMC-(1-77) and its biosynthetic derivative, N-POMC-(1-49) on adrenal growth and on the expression of adrenal steroidogenic enzymes in the late gestati on sheep fetus. Twenty-seven pregnant ewes were used in this study. Fetal v ascular catheters were inserted between 116-125 days gestation, and purifie d bovine N-POMC-(1-77) (1-77) (2 mu g/ml h), N-POMC-(1-49) (2 mu g/ml;h) an d saline were each infused for 48 h between 136 and 138 days gestation. Int rafetal infusion of N-POMC-(1-77) resulted in an increased adrenal/fetal bo dy weight ratio (94.6 +/- 5.7 mg/kg) compared with that in saline-infused ( 75.6 +/- 1.8 mg/kg), but not N-POMC-(1-49)-infused (82.7 +/- 6.1 mg/kg), fe tal sheep. The ratio of CYP17 messenger RNA (mRNA) to 18S ribosomal RNA was also significantly higher in fetal adrenals of the N-POMC-(1-77)-infused g roup (49.1 +/- 4.7) compared with that in either the N-POMC-(1-49)infused ( 20.4 +/- 6.4) or saline-infused (15.2 +/- 4.4) group. There was no differen ce, however, in the ratios of adrenal CYP11A1 mRNA/3 beta-hydroxysteroid de hydrogenase/Delta(5),Delta(4)-isomerase mRNA and CYP21A1 mRNA/18S ribosomal RNA among the N-POMC-(1-77)-, N-POMC-(1-49)-, and saline-infused groups. T here was also no significant change in either plasma cortisol or ACTH conce ntrations in response to the infusion of either N-POMC-(1-77) or N-POMC-(1- 49). In summary, intrafetal infusion of N-POMC-(1-77) stimulated fetal adre nal growth and resulted in a specific increase in adrenal CYP17 gene expres sion in late gestation. N-POMC-(1-77) may therefore play a modulatory role in the increase in fetal adrenal growth and steroidogenesis that occurs bef ore birth.