We examined the effects of 17α-estradiol, the biologically inactive stereoisomer of 17β-estradiol, on cell growth and cell cycle kinetics using the normalized mouse TM3 Leydig cells. A significant biphasic stimulatory growth response was observed by 17α-estradiol exposure with peaks at 1 pg/ml (157.13%) and 100 ng/ml (120.04%) (p<0.05). The growth stimulatory effects of 17α-estradiol were inhibited by tamoxifen. A significant decrease in cell cycle time of Leydig cells exposed to 17α-estradiol was observed in treated cells (p<0.05). RT-PCR analysis indicated that exposure to Leydig cells to 1 pg/ml and 100 ng/ml 17α-estradiol resulted in a 10- and 5-fold increases in the expression of ERα, respectively. Similar effects were observed with exposure to equivalent concentrations of 17β-estradiol. Difference in sensitivity to stereoisomers of estradiol to growth response of Leydig cells did not correlate with the elevated expression of ERα. We conclude that the TM3 Leydig cells are sensitive to the non-typical estrogen, 17α-estradiol, presumably through the activation of ER-independent signaling transduction pathways.

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