Urocortin is not a significant regulator of intermittent electrofootshock-induced adrenocorticotropin secretion in the intact male rat

Urocortin (Ucn) is a newly identified mammalian member of the CRF family of peptides. Ucn activates CRF receptors (both CRF-R1 and CRF-RB) with greate r potency than CRF itself, suggesting that Ucn may play an endogenous role in eliciting (at least some) CRF receptor-mediated events. Because the most characterized physiological function of CRF receptors is the activation of pituitary ACTH secretion, we have compared the effects and potential endog enous roles of CRF and Ucn in regulating plasma ACTH concentrations in inta ct male rats. Synthetic rat Ucn injected iv (0.09-9.0 nmol/kg) elicited ACT H secretion in a dose-dependent manner, causing greater ACTH secretion than CRF at each dose tested. The increases in plasma ACTH concentrations produ ced by CRF or Ucn were virtually abolished by pretreatment with the CRF rec eptor antagonist, astressin (3 mg/kg), and were partially attenuated (by 27 -37%) by an anti-arginine vasopressin serum. These data indicate that both Ucn and CRF elicit ACTH secretion via CRF receptor-dependent mechanisms, an d that the ACTH-releasing activities of both CRF and Ucn are potentiated by endogenous arginine vasopressin. Intravenous administration of rabbit anti -Ucn serum, which inhibited ACTH secretion produced by Ucn, but not CRF, ha d no statistically significant effect on either resting (midday) plasma ACT H concentrations or the rise in ACTH levels elicited by 30 min of intermitt ent electrofootshocks. By contrast, treatment with a rabbit anti-CRF serum that specifically inhibited the ACTH response to CRF lowered plasma concent rations in control unstressed rats and largely prevented the plasma ACTH re sponse to electrofootshocks. These data indicate that although Ucn is a mor e potent ACTH secretagogue than CRF in the intact male rat, it is not a maj or endogenous regulator of pituitary ACTH secretion under basal (midday) co nditions or during acute footshock stress.