PEPTIDE GENE ACTIVATION, SECRETION, AND STEROID FEEDBACK DURING STIMULATION OF RAT NEUROENDOCRINE CORTICOTROPIN-RELEASING HORMONE NEURONS

We have used colloid-induced hypovolemia to investigate mechanisms ope rating in CRH neuroendocrine neurons of the hypothalamic paraventricul ar nucleus during a sustained stress. Specifically, three questions ha ve been addressed using in situ hybridization and RIA. 1) Do neuropept ide secretion and gene activation share the same stimulus threshold? 2 ) Does corticosterone modulate mechanisms regulating CRH gene expressi on during sustained stress? 3) How are neuropeptides commonly colocali zed with CRH affected? Our results show that the secretion of ACTH and activation of the CRH gene have distinct and separate stimulus thresh olds. The threshold is higher for CRH gene activation than for ACTH se cretion, suggesting some degree of mechanistic separation. In addition , corticosterone secreted during the first 3 h of sustained hypovolemi a does not inhibit CRH gene expression. However, feedback inhibition m ay occur in the delayed time domain. Finally, neuropeptides colocalize d with CRH are differentially regulated by sustained hypovolemia. Proe nkephalin messenger RNA levels show a slower temporal response than th ose of CRH, while the vasopressin gene is not activated at any time in parvicellular neuroendocrine neurons. Our results emphasize that CRH neuroendocrine neurons respond to a stress event in a stimulus-specifi c manner in terms of both the profiles of secretion and gene expressio n, and the structure of glucocorticoid feedback.