Corticotropin-Releasing Factor Regulates Proopiomelanocortin Messenger Ribonucleic Acid Levels in vivo

Abstract

Ovine corticotropin-releasing factor (oCRF) was administered to male rats for 3–15 days. Continuous intravenous infusion, repeated subcutaneous, and intracerebroventricular injections of oCRF resulted in a 50–100% increase in messenger ribonucleic acid (mRNA) coding for proopiomelanocortin (POMC) in the anterior pituitaries (AP) of these animals. The synthetic glucocorticoid, dexamethasone, reversed the actions of oCRF. None of the above treatments altered POMC mRNA content in the neurointermediate lobe. Bilateral adrenalectomy enhanced POMC mRNA levels 4.8-fold. To determine whether this effect was dependent on increased hypothalamic production and release of CRF, a bilateral ablation of the paraventricular nucleus (PVN), known to contain CRF neurons directly involved in ACTH secretion, was performed. 6 days after the PVN destruction a parallel 75% reduction of both stalk-median eminence CRF-like immunoreactivity and plasma ACTH had occurred. The AP content of POMC mRNA decreased by 53%, while the ACTH content increased by 56%. These observations suggest that CRF regulates the biosynthesis of POMC-derived polypeptide products in the AP, while the peptide does not seem to be directly involved in intermediate lobe POMC biosynthesis. The reduction of POMC mRNA levels following PVN destruction demonstrates that CRF and other substances located in the nucleus may cause the increased POMC gene transcription following adrenalectomy.