N-proopiomelanocortin (1-77) suppresses expression of steroidegenic 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 steroidogenesis during the last 10-15 days gestation. Recently, we have shown that infusion of POMC (1-77) increases fetal adrenal growth and expression of CYP17 mRNA but does not significantly alter fetal plasma cortisol concentrations [1]. We therefore investigated the effects of infusion of bovine POMC (1-77) and its biosynthetic derivative POMC (1-49) on adrenal StAR mRNA expression. At 136d gestation, POMC (1-77) (n=5 fetuses; 2microg/ml/h), POMC (1-49) (n=5 fetuses, 2microg/ml/h) or Saline (n=5 fetuses, 1ml/h) was infused for 48h. At 138d, fetal adrenal glands were collected and frozen in liquid N2 until RNA was extracted. Northern blot analyses demonstrated a major transcript for StAR mRNA at 3.0kb in fetal adrenal glands from all treatments. The membrane was stripped and re-probed with a P-labelled rat 18S rRNA oligo-probe to verify equal RNA loading. Infusion of POMC (1-77), but not POMC (1-49), resulted in a suppression of fetal adrenal StAR mRNA:18S rRNA when 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.C. L. Coulter, J. T. Ross, M. D. Salkeld, H. P. J. Bennett, S. James and I. C. McMille