Turnbull A V, Vaughan J, Rivier J E, Vale W W, Rivier C
The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California 92037, USA.
Endocrinology. 1999 Jan;140(1):71-8. doi: 10.1210/endo.140.1.6419.
Urocortin (Ucn) is a newly identified mammalian member of the CRF family of peptides. Ucn activates CRF receptors (both CRF-R1 and CRF-R2) with greater 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 endogenous roles of CRF and Ucn in regulating plasma ACTH concentrations in intact male rats. Synthetic rat Ucn injected i.v. (0.09-9.0 nmol/kg) elicited ACTH secretion in a dose-dependent manner, causing greater ACTH secretion than CRF at each dose tested. The increases in plasma ACTH concentrations produced by CRF or Ucn were virtually abolished by pretreatment with the CRF receptor antagonist, astressin (3 mg/kg), and were partially attenuated (by 27-37%) by an antiarginine vasopressin serum. These data indicate that both Ucn and CRF elicit ACTH secretion via CRF receptor-dependent mechanisms, and 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, had no statistically significant effect on either resting (midday) plasma ACTH concentrations or the rise in ACTH levels elicited by 30 min of intermittent electrofootshocks. By contrast, treatment with a rabbit anti-CRF serum that specifically inhibited the ACTH response to CRF lowered plasma concentrations in control unstressed rats and largely prevented the plasma ACTH response to electrofootshocks. These data indicate that although Ucn is a more potent ACTH secretagogue than CRF in the intact male rat, it is not a major endogenous regulator of pituitary ACTH secretion under basal (midday) conditions or during acute footshock stress.
尿皮质素（Ucn）是促肾上腺皮质激素释放因子（CRF）肽家族新发现的哺乳动物成员。Ucn激活CRF受体（CRF-R1和CRF-R2）的效力比CRF本身更强，这表明Ucn可能在引发（至少部分）CRF受体介导的事件中发挥内源性作用。由于CRF受体最具特征的生理功能是激活垂体促肾上腺皮质激素（ACTH）分泌，我们比较了CRF和Ucn在调节完整雄性大鼠血浆ACTH浓度方面的作用及潜在内源性作用。静脉注射合成大鼠Ucn（0.09 - 9.0 nmol/kg）以剂量依赖方式引发ACTH分泌，在每个测试剂量下引起的ACTH分泌均比CRF更多。CRF受体拮抗剂阿斯特辛（3 mg/kg）预处理几乎完全消除了CRF或Ucn引起的血浆ACTH浓度升高，抗精氨酸加压素血清使其部分减弱（27 - 37%）。这些数据表明，Ucn和CRF均通过CRF受体依赖性机制引发ACTH分泌，并且内源性精氨酸加压素增强了CRF和Ucn的促ACTH释放活性。静脉注射兔抗Ucn血清可抑制Ucn而非CRF产生的ACTH分泌，对静息（中午）血浆ACTH浓度或30分钟间歇性电休克引起的ACTH水平升高均无统计学显著影响。相比之下，用特异性抑制对CRF的ACTH反应的兔抗CRF血清处理，可降低对照未应激大鼠的血浆浓度，并在很大程度上阻止了血浆ACTH对电休克的反应。这些数据表明，尽管在完整雄性大鼠中Ucn作为ACTH促分泌剂比CRF更有效，但在基础（中午）条件下或急性足部电击应激期间，它并非垂体ACTH分泌的主要内源性调节因子。
