HEMORRHAGE-INDUCED SECRETION OF CORTICOTROPIN-RELEASING FACTOR-LIKE IMMUNOREACTIVITY INTO THE RAT HYPOPHYSEAL PORTAL CIRCULATION AND ITS INHIBITION BY GLUCOCORTICOIDS

A paradigm for reliably stimulating ACTH secretion in urethane-anesthetized male rats was used to examine hypothalamic secretion of corticotropin-releasing factor-like immunoreactivity (CRF-LI) into the hypophyseal portal circulation. Hemorrhage of 15% estimated blood volume evoked a maximal 4.6-fold elevation in circulating ACTH levels from an initial level of 178.4 .+-. 51.2 (.+-. SE) to 814.7 .+-. 184.6 pg ml-1. The cumulative amount of ACTH secreted in response to hemorrhage was 10-fold greater than the cumulative amount of ACTH secreted by nonhemorrhaged rats (unweighted cumulative effect over all time points). In another experiment from a similarly hemorrhaged group, the hypophyseal portal plasma CRF-LI concentration rose 2-fold from an initial level of 429.7 .+-. 34.2 to 839.3 .+-. 170.4 pg ml-1. Pretreatment with dexamethasone (100 .mu.g/kg body wt, i.m.) had no effect on initial levels of either CRF-LI or ACTH. The hemorrhage-induced elevations of both CRF-LI and ACTH were abolished in dexamethasone-treated rats. The secretory rate of CRF-LI was calculated to be 1.61 .+-. 0.7 pg min-1 in nonhemorrhaged animals. Reversible pharmacological hyperpolarization of the paraventricular nuclei by stereotaxically microinjected procaine (15 .mu.g/100 nl) reduced portal plasma CRF-LI and peripheral plasma ACTH to undetectable levels. CRF-LI is an important hypothalamic regulator of adenohypophyseal ACTH secretion; CRF-LI in the hypophyseal portal circulation is derived from CRF-LI-containing neurons within the paraventricular nuclei; and glucorticoid negative feedback effects can be exerted at the central level.