Gender-related differences in androgen regulation of thromboxane A(2) receptors in rat aortic smooth-muscle cells

Thromboxane A(2) (TXA(2)) has been implicated as an important mediator of cardiovascular diseases. Aortas obtained from male rats are more sensitive to TXA(2) mimetics compared with those obtained from females. A similar phenomenon has been reported in canine coronary arteries. To determine whether there is a gender-related difference in the regulation of TXA(2) receptors by androgenic steroids, we determined the effect of testosterone and dihydrotestosterone (DHT) on TXA(2) receptor density in cultured rat aortic smooth muscle (RASM) cells and guinea pig coronary artery smooth-muscle (CASM) cells. TXA(2) receptor density (B-max) and dissociation constant (K-d) were determined by radioligand binding studies with I-125-BOP, a TXA(2) receptor agonist. Testosterone significantly (p < 0.05) increased TXA(2) receptor density in cultured RASM cells and guinea pig CASM cells. DHT significantly (p < 0.005) increased the B-max in male RASM cells (62 +/- 2 vs. 40 +/- 3 fmol/mg protein; n = 7; p < 0.005). DHT increased the B-max values in both male and female RASM cells, but the increase was significantly (p < 0.05) less in female than in male RASM cells (57 +/- 10% increase for male and 31 +/- 5% for female). Androgen-receptor protein was detected in RASM cells by Western blot and was less in the female RASM cells than in the male. The results indicate that RASM cells possess an androgen receptor and that gender-related differences exist in the regulation of expression of TXA(2) receptors by androgens.