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

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.