Matsuda K, Mathur R S, Ullian M E, Halushka P V
Department of Pharmacology, Medical University of South Carolina, Charleston 29425, USA.
Prostaglandins. 1995 Mar;49(3):183-96. doi: 10.1016/0090-6980(95)00020-b.
Thromboxane A2 (TXA2) has been implicated as an important mediator of cardiovascular diseases, and male rat aortas are reported to be more sensitive to it than female aortas. The effects of sex steroids to regulate the expression of TXA2 receptors in cultured male rat aortic smooth muscle cells (RASMC) were determined. TXA2 receptor density (Bmax) and affinity (Kd) were determined via radioligand binding studies with [125I]BOP, a TXA2 receptor agonist. Testosterone increased Bmax in a concentration-dependent manner without any significant change in Kd. Cycloheximide, actinomycin D, and the 5 alpha-reductase inhibitor L645,390 significantly (P < 0.01) blocked the effect of testosterone. Dihydrotestosterone, the active metabolite of testosterone, increased Bmax and was more potent than testosterone. To determine if there is a sex-related difference in response to testosterone, its effect in cultured female RASMC was assessed. Testosterone increased Bmax in female RASMC but the increase was significantly (P < 0.001) less than that seen in male RASMC. These results indicate that androgenic steroids regulate the expression of vascular TXA2 receptors.
血栓素A2（TXA2）被认为是心血管疾病的重要介质，据报道雄性大鼠主动脉对其比雌性主动脉更敏感。本研究测定了性类固醇对培养的雄性大鼠主动脉平滑肌细胞（RASMC）中TXA2受体表达的调节作用。通过用TXA2受体激动剂[125I]BOP进行放射性配体结合研究，测定TXA2受体密度（Bmax）和亲和力（Kd）。睾酮以浓度依赖性方式增加Bmax，而Kd无显著变化。环己酰亚胺、放线菌素D和5α-还原酶抑制剂L645,390显著（P < 0.01）阻断了睾酮的作用。睾酮的活性代谢产物双氢睾酮增加了Bmax，且比睾酮更有效。为了确定对睾酮的反应是否存在性别相关差异，评估了其在培养的雌性RASMC中的作用。睾酮增加了雌性RASMC中的Bmax，但增加幅度显著（P < 0.001）低于雄性RASMC。这些结果表明雄激素类固醇调节血管TXA2受体的表达。
