Gender-Related Differences in Androgen Regulation of Thromboxane A2 Receptors in Rat Aortic Smooth-Muscle Cells

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Abstract
Thromboxane A2 (TXA2) has been implicated as an important mediator of cardiovascular diseases. Aortas obtained from male rats are more sensitive to TXA2 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 TXA2 receptors by androgenic steroids, we determined the effect of testosterone and dihydrotestosterone (DHT) on TXA2 receptor density in cultured rat aortic smoothmuscle (RASM) cells and guinea pig coronary artery smoothmuscle (CASM) cells. TXA2 receptor density (Bmax) and dissociation constant (Kd) were determined by radioligand binding studies with 125I-BOP, a TXA2 receptor agonist. Testosterone significantly (p < 0.05) increased TXA2 receptor density in cultured RASM cells and guinea pig CASM cells. DHT significantly (p < 0.005) increased the Bmax in male RASM cells (62 ± 2 vs. 40 ± 3 fmol/mg protein; n = 7; p < 0.005). DHT increased the Bmax 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 genderrelated differences exist in the regulation of expression of TXA2 receptors by androgens.