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 ( K d 7.37 nM, B max 10.59 fmol/mg protein) and dihydrotestosterone (DHT; K d 4.89 nM, B max 11.37 fmol/mg protein) in VSMC. Measurement of 5α-reductase activity suggested that testosterone is converted to DHT in VSMC ( K m 0.36 μM, V max 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.
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