Ali Hassan

Z. Wu, H. Ji, A. Hassan, G. Aguilera & K. Sandberg

Center for the Study of Sex Differences, Georgetown University, Washington, DC 20057, USA.

Long-term adrenalectomy (ADX) is associated with marked down-regulation of pituitary corticotropin releasing factor type-1 receptors (CRF-R1) but normal CRF-R1 mRNA levels, suggesting that regulation of receptor levels occurs at post-transcriptional sites. We have reported that adrenal cytosolic proteins, which bind to cis elements in the 5′ leader sequence (5’LS) of the rat angiotensin II type 1a receptor (AT_1aR) mRNA, participate in the regulation of AT_1aR density by inhibiting AT_1aR mRNA translation. In this study, we examined anterior pituitary cytosolic proteins that form RNA protein complexes (RPC) with the 5’LS of the CRF-R1 and the AT_1aR. Competition studies and ultraviolet-crosslinking analysis suggest that formation of CRF-R1 and AT_1aR 5’LS RPC require at least some proteins that are common to both receptor mRNAs. Pituitaries isolated from male Sprague-Dawley rats six days after ADX showed significant (P < 0.05) increases of 2.9-fold in CRF-R1 5’LS RNA binding protein (BP) activity compared to pituitaries from sham-operated rats; this effect of ADX was prevented by glucocorticoid replacement. By contrast, no differences in the number of pituitary AT_1aR binding sites or pituitary AT_1aR 5’LS BP activity were observed between sham and ADX rats, indicating that the effect of ADX on RPC formation was specific for CRF-R1 mRNA. Addition of pituitary cytosolic extracts inhibited in vitro translation of CRF-R1 mRNA by 79% under conditions that had no significant effects on the translation of a control mRNA. The data suggest that CRF-R1 translation is regulated by modulation of the HPA axis through pituitary cytosolic proteins binding to the CRF-R1 5’LS.

Journal of Neuroendocrinology, 16:214-220, 2004