CORTICOTROPIN-RELEASING FACTOR ALONE, BUT NOT ARGININE-VASOPRESSIN ALONE, STIMULATES THE RELEASE OF ADRENOCORTICOTROPIN IN THE CONSCIOUS INTACT SHEEP

These studies compared the relative potencies of CRF and arginine vaso pressin (AW) as ACTH secretagogues in the sheep. Dose-response curves to CRF (10, 25, 50, and 100 mu g/h) and AVP (0.3, 1.0, 3.0, and 10.0 m u g/h) were obtained in five adult sheep, with arterial blood samples taken for CRF, AVP, ACTH, and cortisol measurements to determine the p ituitary-adrenal response. It was found that the first dose of CRF inc reased plasma CRF levels to 444 +/- 79 pg/ml. ACTH levels rose signifi cantly from 28 +/- 5 to 186 +/- 46 pg/ml, with a concurrent rise in co rtisol levels from 7 +/- 3 to 44 +/- 9 ng/ml. Although plasma ACTH and cortisol levels remained elevated, higher doses of CRF failed to prod uce further increases. AVP, at all of the doses studied, did not produ ce an increase in ACTH levels, although cortisol levels rose significa ntly by the second dose. In a second series of experiments, animals re ceived a continuous infusion of CRF (10 mu g/h) alone or in combinatio n with graded doses of AVP (0.3, 1.0, 3.0, and 10.0 mu g/h for 60 min each). It was found that AVP at the highest dose was able to potentiat e the ACTH response to CRF. Lower doses of AVP, which did not stimulat e a further increase in ACTH levels were, however, associated with a s ignificant rise in cortisol levels. In conclusion, it was found that a lthough CRF alone was a potent stimulator of ACTH secretion, AVP at th e doses studied was not able to elicit an ACTH response in the conscio us intact sheep. However, a dose of AVP that was not stimulatory in it self was able to augment the ACTH response to CRF.