Leptin exerts proliferative and anti-apoptotic effects on goose granulosa cells through the PI3K/Akt/mTOR signaling pathway. Issue 149 (May 2015)

• Record Type: Journal Article
• Authors: Wen, Rui; Hu, Shenqiang; Xiao, Qihai; Han, Chunchun; Gan, Chao; Gou, Hua; Liu, Hehe; Li, Liang; Xu, Hengyong; He, Hua; Wang, Jiwen
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 149(2015)
• Page Start: 70
• Page End: 79
• Publication Date: 2015-05
• Subjects: Akt serine/threonine-kinases -- AMPK 5′-AMP-activated protein kinase -- BrdU bromodeoxyuridine -- CCK-8 cell counting kit-8 -- IRS insulin receptor substrates -- JAK/STAT Janus kinase/signal transducer and activator of transcription -- Lepr leptin receptor -- MAPK mitogen-activated protein kinase -- mTOR mammalian target of rapamycin -- PDK1 3-phosphoinositide-dependent kinase -- PI3K phosphatidylinositol 3-kinase -- PIP2 phosphatidylinositol-4, 5-bisphosphate -- PIP3 phosphatidylinositol-3, 4, 5-trisphosphate -- p-S6K phosphorylated S6 kinase -- qRT-PCR quantitative real-time PCR -- S6K S6 kinase -- TUNEL TdT-mediated dUTP nick-end labeling; Leptin -- PI3K -- mTOR -- Proliferation -- Apoptosis -- Goose; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2015.01.001
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: Leptin exerts proliferative and anti-apoptotic effects on goose granulosa cells. The mechanism involves the activation of the PI3K/Akt/mTOR signaling pathway. Leptin exerts its effects by regulating expression of its receptor. Abstract: Leptin was known as a pivotal regulator for the control of food intake and energy expenditure. However, leptin has also been found to be involved in the regulation of female reproductive system through interactions with pathways in the hypothalamic–hypophyseal axis and direct action at the ovarian level. In the present study, granulosa cells from goose ovarian preovulatory (F1-F3) follicles were cultured with leptin (0, 1, 10 or 100 ng/ml). The proliferative and anti-apoptotic actions of leptin in granulosa cells were revealed by CCK-8, BrdU and TUNEL assays. Quantitative real-time PCR and Western blot analyses further indicated that leptin treatment led to increased expression of cyclin D1, cyclin D2, cyclin D3 and bcl-2, and decreased expression of p21 and caspase-3. The effects were involved in the activation of the PI3K/Akt/mTOR signaling pathway, as leptin treatment enhanced the expression of PI3K, Akt1, Akt2, Raptor, mTOR, S6K and p-S6K. Moreover, blockade of the PI3K/Akt/mTOR pathway attenuated the influences of leptin on proliferation and apoptosis of granulosa cells, considering that activated factors by leptin were inhibited in the presence of either 20 μM LY294002 (a PI3K inhibitor) or 10 μM rapamycin (an mTOR inhibitor). In addition, leptin had a modulatory effect on the expression of its receptor at the transcriptional and translational levels, and blockade of PI3K/Akt/mTOR inhibited both basal and leptin-induced Lepr gene and protein expression. These findings suggest that leptin exerts its proliferative and anti-apoptotic effects on goose granulosa cells through the PI3K/Akt/mTOR signaling pathway via interaction with its receptor.