Pournajafi Nazarloo Hossein, Tanaka Yasushi, Dorobantu Maria, Hashimoto Kozo
Second Department of Internal Medicine, Kochi Medical School, Kohasu, Okoh-cho, Nankoku 783-8505, Japan.
Regul Pept. 2003 Sep 15;115(2):131-8. doi: 10.1016/s0167-0115(03)00150-2.
The actions of corticotropin-releasing hormone (CRH) and the related peptides are coordinated by two receptors, CRH receptor type 1 (CRH-R1) and CRH receptor type 2 (CRH-R2). In this study, we examined the effects of CRH deficiency and/or stress due to physically restraint or lipopolysaccharide (LPS) administration on expression of transcripts for CRH-R2 (CRH-R2 mRNA) as well as urocortin (UCN) mRNA in the atria and ventricle using female and male CRH-deficient (knockout, KO) mice. We show that restraint stress caused a significant increase in plasma corticosterone levels in female CRH KO mice, but LPS administration induced a significant increase in plasma corticosterone levels in both female and male CRH KO mice. CRH deficiency caused a robust decrease in basal levels of CRH-R2 mRNA and a significant increase of UCN mRNA expression in the atria and ventricle of female as well as male mice. Restraint stress markedly reduced CRH-R2 mRNA and increased UCN mRNA expression on atria as well as ventricle in both female and male wild-type (WT) mice. Following LPS injection to both female and male mice, CRH-R2 mRNA expression was decreased and UCN mRNA expression was increased in the atria and ventricle of both WT and CRH KO mice in each sex. We speculate that stress or lack of CRH may increase urocortin, which in turn down-regulates CRH-R2 mRNA expression in the heart. These data indicate: (1) that lack of CRH may decreases cardiac CRH-R2 mRNA expression in basal state, (2) that inhibitory effect of CRH deficiency on cardiac CRH-R2 mRNA expression in stress condition seems to be more closely linked to type of stressor than rise in plasma corticosterone level.
促肾上腺皮质激素释放激素（CRH）及相关肽的作用由两种受体协调，即1型CRH受体（CRH-R1）和2型CRH受体（CRH-R2）。在本研究中，我们使用雌性和雄性CRH缺陷（基因敲除，KO）小鼠，研究了CRH缺乏和/或因身体束缚或注射脂多糖（LPS）所致应激对心房和心室中CRH-R2转录本（CRH-R2 mRNA）以及尿皮质素（UCN）mRNA表达的影响。我们发现，束缚应激导致雌性CRH基因敲除小鼠血浆皮质酮水平显著升高，但注射LPS可使雌性和雄性CRH基因敲除小鼠的血浆皮质酮水平均显著升高。CRH缺乏导致雌性和雄性小鼠心房和心室中CRH-R2 mRNA的基础水平大幅降低，UCN mRNA表达显著增加。束缚应激显著降低了雌性和雄性野生型（WT）小鼠心房和心室中CRH-R2 mRNA的表达，并增加了UCN mRNA的表达。对雌性和雄性小鼠注射LPS后，各性别野生型和CRH基因敲除小鼠的心房和心室中CRH-R2 mRNA表达均降低，UCN mRNA表达均增加。我们推测，应激或CRH缺乏可能会增加尿皮质素，进而下调心脏中CRH-R2 mRNA的表达。这些数据表明：（1）CRH缺乏可能会降低基础状态下心脏中CRH-R2 mRNA的表达；（2）应激条件下CRH缺乏对心脏CRH-R2 mRNA表达的抑制作用似乎与应激源类型的关系比与血浆皮质酮水平升高的关系更为密切。
