Infusion of N-Proopiomelanocortin-(1–77) Increases Adrenal Weight and Messenger Ribonucleic Acid Levels of Cytochrome P450 17α-Hydroxylase in the Sheep Fetus during Late Gestation*

Abstract

In the sheep there is a rapid increase in fetal adrenal growth and steroidogenesis 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 role in compensatory adrenal growth and in potentiation of ACTH-induced steroidogenesis. We therefore investigated the effects of infusion of bovine N-POMC-(1-77) and its biosynthetic derivative, N-POMC-(1-49) on adrenal growth and on the expression of adrenal steroidogenic enzymes in the late gestation sheep fetus. Twenty-seven pregnant ewes were used in this study. Fetal vascular catheters were inserted between 116-125 days gestation, and purified bovine N-POMC-(1-77) (2 microg/ml x h), N-POMC-(1-49) (2 microg/ml x h) and saline were each infused for 48 h between 136 and 138 days gestation. Intrafetal infusion of N-POMC-(1-77) resulted in an increased adrenal/fetal body 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), fetal sheep. The ratio of CYP17 messenger RNA (mRNA) to 18S ribosomal RNA was also significantly higher in fetal adrenals ofthe N-POMC-(1-77)-infused group (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 difference, however, in the ratios of adrenal CYP11A1 mRNA/3beta-hydroxysteroid dehydrogenase/delta5,delta4-isomerase mRNA and CYP21A1 mRNA/18S ribosomal RNA among the N-POMC-(1-77)-, N-POMC-(1-49)-, and saline-infused groups. There was also no significant change in either plasma cortisol or ACTH concentrations 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 adrenal growth and resulted in a specific increase in adrenal CYP17 gene expression in late gestation. N-POMC-(1-77) may therefore play a modulatory role in the increase in fetal adrenal growth and steroidogenesis that occurs before birth.