TESTOSTERONE INCREASES THROMBOXANE A(2) RECEPTOR DENSITY AND RESPONSIVENESS IN RAT AORTAS AND PLATELETS

Testosterone has been implicated as a risk factor for cardiovascular d iseases. Thromboxane (Tx) Az is an important pathophysiological mediat or for thrombotic vascular diseases. This study investigated the effec ts of testosterone on platelet and vascular TxA(2) receptors. Male rat s were treated with either testosterone cypionate for 2 wk, sham opera ted, castrated, or castrated and treated with testosterone cypionate f or 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 aort ic 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 bet a(5Z),3 alpha(1E,3R()),4 alpha)]-7-(3-(3-hydroxy-4-(4'-iodophe tenyl) -7-oxabicyclo[2.2.1]heptan-2-yl]-5-heptenoic acid (I-BOP), to induce p latelet 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 s ignificantly (P < 0.05) greater maximum aortic contractile response to the TxA(2) mimetic, U-46619, compared with intact rats. Castration re sulted 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 s ignificantly reversed by testosterone treatment (89.2 +/- 7.1 fmol/mg protein; n = 4). Castration resulted in a significantly (P < 0.05) low er maximal aortic contractile response that was reversed by treatment with testosterone. Castration did not significantly change platelet Tx A(2) receptor density. This study demonstrates that testosterone regul ates the expression of platelet and vascular TxA(2) receptors. The res ults raise the possibility that TxA(2) receptors mediate a component o f the thrombogenicity of testosterone.