Androgen receptors, 5 alpha-reductase activity and androgen-dependent proliferation of vascular smooth muscle cells

Abstract

To assess the direct effect of androgen on the development of atherosclerosis, we investigated the effect of androgen and its receptor expression in rat vascular smooth muscle cells (VSMC) isolated from rat aorta. We detected the androgen receptor mRNA in VSMC by reverse transcription of the total RNA coupled with amplification of the resulting cDNA by polymerase chain reaction. Binding studies revealed the presence of a single class of binding sites for testosterone (Kd 7.37 nM, Bmax 10.59 fmol/mg protein) and dihydrotestosterone (DHT; Kd 4.89 nM, Bmax 11.37 fmol/mg protein) in VSMC. Measurement of 5 alpha-reductase activity suggested that testosterone is converted to DHT in VSMC (Km 0.36 microM, Vmax 623 fmol/mg protein/h). Moreover, in the present study, DHT significantly stimulated DNA synthesis of VSMC (120-160% of control). The mitogenic activity of testosterone is much less potent than that of DHT. Considering these results, we concluded that androgen may directly accelerate atherosclerosis by stimulating the proliferation of VSMC.