Sex steroid hormone receptors play a central role in modulating telomerase activity, especially in cancer cells. However, information on the regulation of steroid hormone receptors and their distinct functions on telomerase activity within the mesenchymal stem cell are largely unavailable due to low telomerase activity in the cell. In this study, the effects of estrogen (E(2)) treatment and function of estrogen receptor alpha (ER alpha) and estrogen receptor beta (ER beta) on telomerase activity were investigated in human mesenchymal stem cells (hMSCs). Telomerase activity and mRNA expression of the catalytic subunit of telomerase (hTERT) were upregulated by treatment of the cells with E2. The protein concentration of ER alpha was also increased by E(2) treatment, and enhancement of ER alpha accumulation in the nucleus was clearly detected with immunocytochemistry. When ER alpha expression was reduced by siRNA transfection into hMSCs, the effect of E(2) on the induction of hTERT expression and telomerase activity was diminished. In contrast, the transient overexpression of ER alpha increased the effect of E(2) on the expression of hTERT mRNA. These findings indicate that the activation of hTERT expression and telomerase activity by E(2) in hMSCs depends on ER alpha, but not on ER beta.

Keywords: AKT1, estrogen receptor, mesenchymal stem cells, telomerase