TESTOSTERONE INCREASES THROMBOXANE A(2) RECEPTOR DENSITY AND RESPONSIVENESS IN RAT AORTAS AND PLATELETS
TESTOSTERONE INCREASES THROMBOXANE A(2) RECEPTOR DENSITY AND RESPONSIVENESS IN RAT AORTAS AND PLATELETS
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DOI：
10.1152/ajpheart.1994.267.3.h887
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发表时间：
1994-09-01
影响因子：
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通讯作者：
HALUSHKA, PV
中科院分区：
文献类型：
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作者：
MATSUDA, K;RUFF, A;HALUSHKA, PV
睾丸素被认为是心血管疾病的危险因素。血栓烷(TX)Az是血栓性血管疾病的重要病理生理介质。本研究探讨了睾酮对血小板和血管TXA(2)受体的影响。雄性大鼠分别给予西柏酸睾丸酮2wk、假手术、去势或去势后给予西柏酸睾丸酮治疗2wk。正常大鼠经睾酮处理后，血小板TXA(2)受体密度显著增加(P<；0.001)，从25.4+/-3.2fmol/mg蛋白增加到42.9+/-4.2fmol/mg蛋白(P<；0.005~86.1+/-6.1fmol/mg蛋白，n=9。4α)]-7-(3-(3-羟基-4-(4‘-碘-noxy)-1-butenyl)-7-oxabicyclo[2.2.1]heptan-2-yl]-5-heptenoic酸，I-BOP)，诱导血小板聚集作用显著(P<；0.01)，从对照组的0.45+/-0.16 nM(n=7)下降到睾酮处理组的0.07+/-0.01 nM(n=13)。与正常大鼠相比，睾酮治疗导致对TXA(2)模拟物U-46619的最大主动脉收缩反应显著增加(P<；0.05)。去势后大鼠主动脉TXA(2)受体密度由51.7+/-3.7降至27.3+/-5.3fmol/mg蛋白(P<；0.01)，而睾酮处理组(89.2+/-7.1fmol/mg蛋白；n=4)可明显逆转此作用。去势可显著降低(P<；0.05)最大主动脉收缩反应，而睾丸激素治疗可逆转这种反应。去势对血小板TXA(2)受体密度无明显影响。这项研究表明，睾酮调节血小板和血管TXA(2)受体的表达。这一结果提出了TXA(2)受体介导睾酮血栓形成的可能性。
Testosterone has been implicated as a risk factor for cardiovascular diseases. Thromboxane (Tx) Az is an important pathophysiological mediator for thrombotic vascular diseases. This study investigated the effects of testosterone on platelet and vascular TxA(2) receptors. Male rats were treated with either testosterone cypionate for 2 wk, sham operated, castrated, or castrated and treated with testosterone cypionate for 2 wk. Treatment of intact rats with testosterone significantly (P < 0.001) increased the TXA(2) receptor density in platelets from 25.4 +/- 3.2 to 42.9 +/- 4.2 fmol/mg protein (P < 0.005, n = 17) and in aortic membranes from 48.7 +/- 1.7 to 86.1 +/- 6.1 fmol/mg protein, n = 9. The threshold concentration of the TxA(2) mimetic, [1S-(1 alpha,2 beta(5Z),3 alpha(1E,3R(*)),4 alpha)]-7-(3-(3-hydroxy-4-(4'-iodophe noxy)-1-butenyl)-7-oxabicyclo[2.2.1]heptan-2-yl]-5-heptenoic acid (I-BOP), to induce platelet aggregation was significantly (P < 0.01) decreased from 0.45 +/- 0.16 nM, n = 7, in the control rats to 0.07 +/- 0.01 nM, n = 13, in the testosterone-treated rats. Testosterone treatment resulted in a significantly (P < 0.05) greater maximum aortic contractile response to the TxA(2) mimetic, U-46619, compared with intact rats. Castration resulted in a significant (P < 0.01) decrease in aortic TxA(2) receptor density from 51.7 +/- 3.7 to 27.3 +/- 5.3 fmol/mg protein, which was significantly reversed by testosterone treatment (89.2 +/- 7.1 fmol/mg protein; n = 4). Castration resulted in a significantly (P < 0.05) lower maximal aortic contractile response that was reversed by treatment with testosterone. Castration did not significantly change platelet TxA(2) receptor density. This study demonstrates that testosterone regulates the expression of platelet and vascular TxA(2) receptors. The results raise the possibility that TxA(2) receptors mediate a component of the thrombogenicity of testosterone.