N-proopiomelanocortin (1-77) suppresses expression of steroidogenic acute regulatory protein (StAR) mRNA in the adrenal gland of the fetal sheep.

In the sheep, there is a rapid increase in fetal adrenal growth and steroid ogenesis during the last 10-15 days gestation. Recently, we have shown that infusion of POMC (1-77) increases fetal adrenal growth and expression of C YP17 mRNA but does not significantly alter fetal plasma cortisol concentrat ions [1]. We therefore investigated the effects of infusion of bovine POMC (1-77) and its biosynthetic derivative POMC (1-49) on adrenal StAR mRNA exp ression. At 136d gestation, POMC (1-77) (n=5 fetuses; 2 mug/ml/h), POMC (1- 49) (n=5 fetuses, 2 mug/ml/h) or Saline (n=5 fetuses, 1ml/h) was infused fo r 48h. At 138d, fetal adrenal glands were collected and frozen in liquid N- 2 until RNA was extracted. Northern blot analyses demonstrated a major tran script for StAR mRNA at 3.0kb in fetal adrenal glands from all treatments. The membrane was stripped and re-probed with a P-32-labelled rat 18S rRNA o ligo-probe to verify equal RNA loading. Infusion of POMC (1-77), but not PO MC (1-49), resulted in a suppression of fetal adrenal StAR mRNA:18S rRNA wh en compared to adrenal StAR mRNA:18S rRNA from saline-infused controls. Our data suggest POMC (1-77) may act via separate mechanisms to increase fetal adrenal growth and to limit adrenal steroidogenesis through suppression of StAR mRNA.