Studies of the Secretion of Corticotropin-Releasing Factor and Arginine Vasopressin into the Hypophysial-Portal Circulation of the Conscious Sheep

TLDR

The study aimed to characterize CRF and AVP secretion into the hypophysial‑portal circulation of conscious sheep. The authors monitored the temporal dynamics of CRF, AVP, ACTH, β‑endorphin, α‑MSH, and cortisol, and assessed how audiovisual stress and insulin‑induced hypoglycemia affect the hypothalamic‑pituitary‑adrenal axis. CRF and AVP are pulsatilely secreted with three distinct pulse patterns; audiovisual stress and hypoglycemia rapidly elevate all measured peptides, yet ACTH secretion does not strictly mirror CRF/AVP release, indicating additional secretagogues, and the altered CRF:AVP ratio during stress highlights AVP’s role as an ACTH secretagogue in sheep.

Abstract

Studies were undertaken to characterize the secretion of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) into the hypophysial-portal circulation of the conscious sheep. In addition, we examined the temporal relationship between the secretion of these two hypothalamic peptides and the secretion of three pro-opiomelanocortin peptides – adrenocorticotropic hormone (ACTH), ir-β-endorphin, and ir-α-melanocyte-stimulating hormone – and cortisol and determined the effects of an audiovisual emotional stimulus and insulin-induced hypoglycemia on the entire hypothalamic-pituitary-adrenal axis. In the basal state, the secretion of CRF, AVP, the three pro-opiomelanocortin peptides, and cortisol was pulsatile in nature, and three CRF and AVP pulse patterns were observed: a concordant increase in CRF and AVP, an isolated rise in CRF, and an isolated increase in AVP. In 4 of the 5 animals, a 3-min audiovisual stress (barking dog) rapidly increased the plasma levels of all the measured substances, although the magnitude and duration of the effect differed markedly between the animals. Insulin-induced hypoglycemia markedly increased AVP and, to a lesser extent, CRF concentrations in portal plasma and thereby altered the CRF:AVP molar ratio. Although pituitary-adrenal activation was closely correlated with the increased hypothalamic activity, a strict 1:1 concordance between CRF/AVP secretion and ACTH secretion was not seen. The anesthetic ketamine selectively increased portal AVP concentrations to levels which exceeded those attained during hypoglycemia and rapidly activated the pituitary-adrenal axis. We conclude the following: (1) CRF and AVP are secreted by the hypothalamus in a pulsatile fashion; (2) ACTH secretion can be stimulated by increases in either CRF or AVP; (3) the absence of a strict 1:1 concordance between hypothalamic CRF/AVP release and pituitary ACTH secretion during stress may be partly due to the release of additional hypothalamic ACTH secretagogues; (4) the ability of both audiovisual stimuli and insulin-induced hypoglycemia to augment CRF and AVP secretion indicates that the paraventricular hypothalamus may be activated by a variety of neural inputs, and (5) the marked alteration of the CRF:AVP molar ratio during stress suggests that AVP may be an important ACTH secretagogue in vivo in the sheep.