Ishizuka Tsuneo, Ito Osamu, Omata Ken, Ito Sadayoshi
Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, Japan.
Nihon Jinzo Gakkai Shi. 2004 Oct;46(7):685-92.
The role of androgens in the production of 20-hydroxyeicosatetraenoic acid (20-HETE) was determined in the kidney of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The renal production of 20-HETE and blood pressure were higher in males than in females at 9 weeks of age. The renal production of 20-HETE was significantly greater in male SHR than in male WKY, whereas it was significantly lower in female SHR than in female WKY. The differences in the renal production of 20-HETE were consistent with the cytochrome P-450 4A protein levels. Plasma free-testosterone levels in male SHR were twice as high as those in male WKY. Castration and treatment with the androgen receptor antagonist, flutamide, reduced blood pressure, the renal production of 20-HETE, and P-450 4A protein levels in both strains. The renal production of 20-HETE was significantly lower in castrated SHR than in castrated WKY. These results indicate that the renal production of 20-HETE and the expression of P-450 4A have gender and strain-differences, and high levels of plasma androgens induce the expression of P-450 4A and the production of 20-HETE in the kidney of male SHR. The androgen-induced production of 20-HETE may be associated with hypertension in male SHR.
研究了雄激素在自发性高血压大鼠（SHR）和Wistar-Kyoto大鼠（WKY）肾脏中对20-羟基二十碳四烯酸（20-HETE）生成的作用。9周龄时，雄性大鼠肾脏中20-HETE的生成量和血压均高于雌性。雄性SHR肾脏中20-HETE的生成量显著高于雄性WKY，而雌性SHR中20-HETE的生成量则显著低于雌性WKY。20-HETE肾脏生成量的差异与细胞色素P-450 4A蛋白水平一致。雄性SHR的血浆游离睾酮水平是雄性WKY的两倍。去势以及用雄激素受体拮抗剂氟他胺治疗可降低两种品系大鼠的血压、肾脏中20-HETE的生成量以及P-450 4A蛋白水平。去势的SHR肾脏中20-HETE的生成量显著低于去势的WKY。这些结果表明，20-HETE的肾脏生成量和P-450 4A的表达存在性别和品系差异，高水平的血浆雄激素可诱导雄性SHR肾脏中P-450 4A蛋白的表达和20-HETE的生成。雄激素诱导的20-HETE生成可能与雄性SHR的高血压有关。
