Hemorrhage-induced secretion of corticotropin-releasing factor-like immunoreactivity into the rat hypophysial portal circulation and its inhibition by glucocorticoids.
A paradigm for reliably stimulating ACTH secretion in urethane-anesthetized male rats has been used to examine hypothalamic secretion of corticotropin-releasing factor-like immunoreactivity (CRF-LI) into the hypophysial 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 hypophysial 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 microgram/kg BW, im) 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 micrograms/100 nl) reduced portal plasma CRF-LI and peripheral plasma ACTH to undetectable levels. These observations led to the following conclusions: 1) CRF-LI is an important hypothalamic regulator of adenohypophysial ACTH secretion, 2) CRF-LI in the hypophysial portal circulation is derived from CRF-LI-containing neurons within the paraventricular nuclei, and 3) glucocorticoid negative feedback effects can be exerted at the central level.
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000097:blood / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D006470:Hemorrhage / Q000503:physiopathology*; D008297:Male; D010903:Pituitary Gland, Anterior / Q000098:blood supply*; D011168:Portal System; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow
D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone