title: Studies of the secretion of corticotropin-releasing factor and arginine vasopressin into the hypophysial-portal circulation of the conscious sheep. I. Effect of an audiovisual stimulus and insulin-induced hypoglycemia.
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-beta-endorphin, and ir-alpha-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.
authors.affiliation: Medical Research Centre, Prince Henry's Hospital, Melbourne, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Engler
authors.forename: T
authors.initials: T
authors.lastname: Pham
authors.forename: M J
authors.initials: MJ
authors.lastname: Fullerton
authors.forename: G
authors.initials: G
authors.lastname: Ooi
authors.forename: J W
authors.initials: JW
authors.lastname: Funder
authors.forename: I J
authors.initials: IJ
authors.lastname: Clarke
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000097:blood / Q000378:metabolism*; D005260:Female; D006854:Hydrocortisone / Q000378:metabolism; D007003:Hypoglycemia / Q000097:blood / Q000503:physiopathology*; D007031:Hypothalamus / Q000378:metabolism*; D010902:Pituitary Gland / Q000098:blood supply* / Q000378:metabolism; D011863:Radioimmunoassay; D012756:Sheep / Q000502:physiology*; D013312:Stress, Physiological / Q000097:blood / Q000503:physiopathology*; D000521:alpha-MSH / Q000378:metabolism; D001615:beta-Endorphin / Q000378:metabolism
chemical_list: D001127:Arginine Vasopressin; D000521:alpha-MSH; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone