Corticotropin‐Releasing Factor But Not Urocortin Is Involved in Adrenalectomy‐Induced Adrenocorticotropin Release

Abstract

Urocortin, a new corticotropin-releasing factor (CRF)-related peptide, has been reported to have the ability to bind to CRF receptors and to stimulate adrenocorticotropin (ACTH) secretion from the rat anterior pituitary in vivo and in vitro. In this study, we examined the effect of intravenous administration of urocortin-antiserum to investigate the role of endogenous urocortin on ACTH secretion from rat anterior pituitary after adrenalectomy. Male Sprague-Dawley rats, which were maintained in a conscious and undisturbed condition, were administered non-immunized rabbit serum (NRS), CRF-antiserum or urocortin-antiserum at a volume of 1 ml/kg b.w. 15 min before the injection of secretagogues. Synthetic rat urocortin (2 microg/kg B.W.) increased plasma ACTH concentrations by about sixfold the basal concentration. The pretreatment with urocortin-antiserum but not CRF-antiserum abolished the urocortin-induced increase in plasma ACTH concentrations. In adrenalectomized rats, plasma ACTH concentrations were markedly increased at basal conditions, and rapidly reduced after the administration of CRF-antiserum. By contrast, administration of urocortin-antiserum did not alter ACTH secretion induced by adrenalectomy. Our results suggest that endogenous urocortin is unlikely to be involved in ACTH release in adrenalectomized rats.

Physiology, pharmacology, and therapeutic relevance of urocortins in mammals: Ancient CRF paralogs

“…Unlike CRF-deficient mice [290], Ucn 1-deficient mice exhibit normal basal and stress-induced HPA hormone levels [292,296]. Similarly, unlike CRF antisera, peripheral administration of specific Ucn 1 antisera does not modify basal, stressinduced or adrenalectomy-induced ACTH levels [179,278]. Finally, unlike the distribution of CRF, Ucn 1-immunoreactive fibers are scarce in the PVN and the external layer of the median eminence under basal conditions [100,101,158].…”

Distribution of urocortin‐like immunoreactivity in the central nervous system of the frog Rana esculenta

“…In mammals, Ucn possesses biological activities similar to those of CRF and urotensin I, and, like CRF, it plays an important role in modifying the efferent components of endocrine, autonomic, immune, and behavioral responses to stress (Turnbull et al, 1996;Turnbull and Rivier, 1997;Skelton et al, 2000b). In rats, intravenous or intracerebroventricular administration of Ucn elevates the plasma adrenocorticotropic hormone (ACTH) levels (Turnbull and Rivier, 1997;Asaba et al, 1998;Masuzawa et al, 1999), which mimics the endocrine responses to endogenous CRF during stress.…”

Urocortin Expression in Rat Brain: Evidence Against a Pervasive Relationship of Urocortin-Containing Projections With Targets Bearing Type 2 CRF Receptors

“…An involvement in pituitary-adrenal regulation is suggested by the findings that UCN is more potent than CRF in promoting ACTH secretion Asaba et al, 1998), along with indications that it may be expressed in parvocellular neurons of the PVH (Kozicz et al, 1998) and strong evidence for expression in the human anterior pituitary (Iino et al, 1997). However, passive immunoneutralization of UCN has been found to affect neither resting plasma ACTH levels nor the increased titers seen in response to footshock stress (Turnbull et al, 1999) or adrenalectomy (Masuzawa et al, 1999). This is compatible with the present findings, which suggest that any direct involvement of UCN in regulating the hypothalamo-pituitaryadrenal axis is apt to be achieved by way of UCN-ir inputs to the paraventricular nucleus, which would not be expected to be accessed by systemically administered immunoglobulins in immunoneutralization experiments.…”