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 μg/ml•h), N-POMC-(1–49) (2μ g/ml•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 of the 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/3β- hydroxysteroid dehydrogenase/Δ5,Δ4-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.