Nakazawa Ryuto, Tanaka Masami, Takahashi Takeshi, Kobayashi Shinichi, Iwamoto Teruaki
Department of Urology, St. Marianna University, Kawasaki, Japan.
Endocr J. 2007 Apr;54(2):211-9. doi: 10.1507/endocrj.k06-134. Epub 2007 Jan 22.
We investigated the effects of castration and androgen administration on angiotensin II receptor mRNA expression and apoptosis related proteins in the rat bladders. Sprague-Dawley rats were divided into three groups: the control group (sham operation; n = 8), the castration group (castrated, 8 weeks old, n = 8) and the castration plus testosterone group (1% testosterone gel administrated percutaneously into the dorsum daily for 8 weeks starting at 4 weeks after castration, n = 8). Bladder total RNA was extracted, and real-time PCR was performed to quantitatively measure the mRNA expression of angiotensin converting enzyme (ACE), angiotensin II (A II) receptor type 1 (AT1 receptor) and A II receptor type II (AT2 receptor). Western blotting was performed to determine the expression of apoptosis-related proteins. Expression of AT2 receptor mRNA and caspase-3 protein significantly increased in the rat bladder after castration, and these increases were reduced to control levels by testosterone administration. These results suggest that expression of AT2 receptor and caspase-3 in the bladder is androgen-dependent. Expression of Bcl-2 and Bax protein in the rat bladder was not altered by castration. Expression of mitogen-activated protein (MAP) kinase phosphatase-1 protein in the rat urinary bladder was significantly increased by castration, but this increase was smaller with testosterone administration. These results suggest that expression of AT2 receptor mRNA and apoptosis-related proteins in the rat urinary bladder are affected by the change of androgen environment. The present study was the first to clarify the relationship between AT2 receptor and androgen in the urinary bladder.
我们研究了去势及雄激素给药对大鼠膀胱中血管紧张素II受体mRNA表达及凋亡相关蛋白的影响。将Sprague-Dawley大鼠分为三组:对照组(假手术;n = 8)、去势组(8周龄去势,n = 8)和去势加睾酮组(去势4周后开始每天经皮在背部涂抹1%睾酮凝胶,持续8周,n = 8)。提取膀胱总RNA,并进行实时PCR以定量测定血管紧张素转换酶(ACE)、血管紧张素II(A II)1型受体(AT1受体)和A II 2型受体(AT2受体)的mRNA表达。进行蛋白质免疫印迹法以测定凋亡相关蛋白的表达。去势后大鼠膀胱中AT2受体mRNA和半胱天冬酶-3蛋白的表达显著增加,而睾酮给药可将这些增加降低至对照水平。这些结果表明膀胱中AT2受体和半胱天冬酶-3的表达是雄激素依赖性的。去势未改变大鼠膀胱中Bcl-2和Bax蛋白的表达。去势显著增加了大鼠膀胱中有丝分裂原活化蛋白(MAP)激酶磷酸酶-1蛋白的表达,但睾酮给药后这种增加较小。这些结果表明大鼠膀胱中AT2受体mRNA和凋亡相关蛋白的表达受雄激素环境变化的影响。本研究首次阐明了膀胱中AT2受体与雄激素之间的关系。