Mechanism of Androgens-Induced Apoptosis on Mouse Embryonic Stem Cells

• Main Authors: Tian-Wang Hsu, 許天旺
• Other Authors: Yan-Der Hsuuw
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/84805621331646523178

碩士 === 國立屏東科技大學 === 畜產系 === 94 === Androgens, principally testosterone (T) and 5α-dihydrotestosterone (DHT), their biological actions are mediated by a ligand-dependent nuclear transcription factor, the androgen receptor (AR). The AR is a member of the steroid hormone receptor family, which is found in the inner cell mass (ICM) of blastocysts and mouse embryonic stem (ES) cells. However, many interesting questions regarding the fundamental mechanism of AR on androgen-regulated in mouse ES cells. In this experiment, we provide a study to investigate the effects and mechanism of androgen-induced apoptosis in mouse embryonic stem (ES) cells. In the effect of androgens on ES cells growth, the results presented here indicate that androgens-induced ES cells apoptosis in vitro. In contrast, the non-steroidal anti-androgen nilutamide significantly blocked androgen-induced apoptosis. Over-expression of AR did not change the ES cells undifferentiation and self-renew markers, Nanog, OCT3/4 and GDF3. However, it increased the expression of cell cycle inhibitors, p27 and p21 and blocked the expression of cyclin D and cyclin E. The enhancing effects of androgens on caspase-3 activity and poly (ADP-ribose) polymerase (PARP) substrates also indicated that activation of caspase cascade might be involved in androgen/AR-promoted ES cell apoptosis. In addition, androgens/AR activated the endoplasmic reticulum (ER) stress-induced pathway of the caspase-12, GRP78 and GRP94 in ES cells apoptosis. On the other hand, androgens-induced apoptosis was not affected the expression of Bcl-2, Bax or Bad. Together, these findings provide a molecular basis signaling pathways of androgen/AR that may help us to better understand the roles of AR in androgens-mediated ES cells apoptosis.