Asaba K, Makino S, Hashimoto K
Second Department of Internal Medicine, Kochi Medical School, Okoh-cho, Nankoku-city, Kochi 783-8505, Japan.
Brain Res. 1998 Sep 21;806(1):95-103. doi: 10.1016/s0006-8993(98)00747-1.
Both urocortin (UCN) and corticotropin-releasing hormone (CRH) are known to stimulate secretion of adrenocorticotropic hormone (ACTH) by corticotroph cells via type-1 corticotropin-releasing hormone receptor (CRHR-1). We extensively examined UCN effects on the anterior pituitary (AP), particularly on proopiomelanocortin (POMC) mRNA and CRHR-1 mRNA as well as ACTH secretion in vivo. Moreover, signal transduction with UCN exposure was assessed in AP cell cultures in comparison with transduction following CRH exposure. Intravenously administered of UCN (5 microg/kg) increased ACTH and corticosterone secretion. Similarly, intravenous administration of UCN increased POMC mRNA and decreased CRHR-1 mRNA in the AP. These UCN effects were more potent and long-lasting than those of CRH. The prominent effect of UCN on ACTH secretion in vivo was confirmed in AP cell cultures, where application of UCN stimulated ACTH release approximately 7 times more strongly than CRH. The effect of UCN on ACTH release was enhanced by phorbol esters which activate protein kinase C, but was reduced by the selective cAMP-dependent protein kinase inhibitor, H-89. These results suggest that, as with CRH, UCN stimulates ACTH production and/or release through cAMP-dependent mechanisms, and that protein kinase C-dependent mechanism has a synergistic effect upon UCN-induced ACTH release. The more potent effects of UCN relative to CRH may be attributable to UCN's higher affinity for CRHR-1.
已知尿皮质素（UCN）和促肾上腺皮质激素释放激素（CRH）均可通过1型促肾上腺皮质激素释放激素受体（CRHR-1）刺激促肾上腺皮质激素（ACTH）细胞分泌促肾上腺皮质激素（ACTH）。我们广泛研究了UCN对垂体前叶（AP）的影响，特别是对阿黑皮素原（POMC）mRNA和CRHR-1 mRNA以及体内促肾上腺皮质激素（ACTH）分泌的影响。此外，与CRH暴露后的转导相比，评估了UCN暴露在AP细胞培养物中的信号转导。静脉注射UCN（5微克/千克）可增加促肾上腺皮质激素（ACTH）和皮质酮的分泌。同样，静脉注射UCN可增加AP中POMC mRNA并降低CRHR-1 mRNA。这些UCN的作用比CRH的作用更强且更持久。在AP细胞培养物中证实了UCN对体内促肾上腺皮质激素（ACTH）分泌的显著作用，其中应用UCN刺激促肾上腺皮质激素（ACTH）释放的强度比CRH高约7倍。佛波酯激活蛋白激酶C可增强UCN对促肾上腺皮质激素（ACTH）释放的作用，但选择性cAMP依赖性蛋白激酶抑制剂H-89可降低该作用。这些结果表明，与CRH一样，UCN通过cAMP依赖性机制刺激促肾上腺皮质激素（ACTH）的产生和/或释放，并且蛋白激酶C依赖性机制对UCN诱导的促肾上腺皮质激素（ACTH）释放具有协同作用。UCN相对于CRH的更强作用可能归因于UCN对CRHR-1的更高亲和力。
