SEX STEROID REGULATION OF THROMBOXANE A(2) RECEPTORS IN CULTURED RAT AORTIC SMOOTH-MUSCLE CELLS

Thromboxane A(2) (TXA(2)) has been implicated as an important mediator of cardiovascular diseases, and male rat aortas are reported to be mo re sensitive to it than female aortas. The effects of sex steroids to regulate the expression of TXA(2) receptors in cultured male rat aorti c smooth muscle cells (RASMC) were determined. TXA(2) receptor density (B-max) and affinity (K-d) were determined via radioligand binding st udies with [I-125]BOP, a TXA(2) receptor agonist. Testosterone increas ed B-max in a concentration-dependent manner without any significant c hange in K-d. Cycloheximide, actinomycin D, and the 5 alpha-reductase inhibitor L645,390 significantly (P < 0.01) blocked the effect of test osterone. Dihydrotestosterone, the active metabolite of testosterone, increased B-max and was more potent than testosterone. To determine if there is a sex-related difference in response to testosterone, its ef fect in cultured female RASMC was assessed. Testosterone increased B-m ax 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 TXA(2) receptors.