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 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.
Coulter
C L
CL
Dept Physiology, University of Adelaide, Australia.
Ross
J T
JT
Salkeld
M D
MD
Bennett
H P
HP
James
S
S
McMillen
I C
IC
D000311:Adrenal Glands / Q000196:embryology*; D000818:Animals; D015152:Blotting, Northern; D005333:Fetus / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D010750:Phosphoproteins / Q000235:genetics*; D011333:Pro-Opiomelanocortin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors*; D012756:Sheep; D000098682:Steroidogenic Acute Regulatory Protein
D010446:Peptide Fragments; D010750:Phosphoproteins; D012333:RNA, Messenger; C421924:pro-opiomelanocortin (1-49); C421923:pro-opiomelanocortin (1-77); D000098682:Steroidogenic Acute Regulatory Protein; D011333:Pro-Opiomelanocortin