| Title: | "mTOR is involved in 17beta-estradiol-induced, cultured immature boar Sertoli cell proliferation via regulating the expression of SKP2, CCND1, and CCNE1" |
| Author(s): | Yang WR; Wang Y; Wang Y; Zhang JJ; Zhang JH; Lu C; Wang XZ; |
| Address: | "College of Animal Science and Technology, Southwest University, Chongqing, P. R. China; Chongqing Key Laboratory of Forage and Herbivore, Southwest University, Chongqing, P. R. China" |
| ISSN/ISBN: | 1098-2795 (Electronic) 1040-452X (Linking) |
| Abstract: | "Mammalian target of rapamycin (mTOR) is known to be involved in mammalian cell proliferation, while S-phase kinase-associated protein 2 (SKP2) plays a vital role in the cell cycle. Within the testis, estrogen also plays an important role in Sertoli cell proliferation, although it is not clear how. The present study asked if mTOR is involved in 17beta-estradiol-dependent Sertoli cell proliferation. We specifically assessed if extracellular signal-regulated kinase 1/2 (ERK1/2) and/or phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) exert convergent effects toward the activation of mTOR signaling, and if this signaling regulates the expression of SKP2 through retinoblastoma (RB) and early mitotic inhibitor 1 (EMI1) protein and on CCNE1 and CCND1 mRNA levels. Treatment with 17beta-estradiol for 15-90 min activated mTOR, with mTOR phosphorylation peaking after 30 min. U0126 (5 muM), a specific inhibitor of (MEK1/2), and 10-DEBC (2 muM), a selective inhibitor of AKT, both significantly reduced 17beta-estradiol-induced phosphorylation of mTOR. Rapamycin suppressed 17beta-estradiol-induced Sertoli cell proliferation, appearing to act by reducing the abundance of SKP2, CCND1, and CCNE1 mRNA as well as RB and EMI1 protein. These data indicated that 17beta-estradiol enhances Sertoli cell proliferation via mTOR activation, which involves both ERK1/2 and PI3K/AKT signaling. Activated mTOR subsequently increases SKP2 mRNA and protein expression by enhancing the expression of CCND1 and CCNE1, and inhibits SKP2 protein degradation by increasing EMI1 abundance" |
| Keywords: | "Analysis of Variance Animals Blotting, Western Cell Proliferation/*physiology Cyclin D1/metabolism Cyclin E/metabolism DNA Primers/genetics Estradiol/*metabolism/pharmacology Gene Expression Regulation/drug effects/*physiology Male Phosphorylation/drug ef;" |
| Notes: | "MedlineYang, Wei-Rong Wang, Yong Wang, Yi Zhang, Jiao-Jiao Zhang, Jia-Hua Lu, Cheng Wang, Xian-Zhong eng Research Support, Non-U.S. Gov't 2015/03/06 Mol Reprod Dev. 2015 Apr; 82(4):305-14. doi: 10.1002/mrd.22473. Epub 2015 Mar 4" |
