Follicle loss and PTEN/PI3K/mTOR signaling pathway activated in LepR-mutated mice

Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology
Hexia XiaWei Zhang

Abstract

Female mice (Y123F) with substitution mutations introduced through homologous gene targeting, replacing the three tyrosine residues of LepR, Tyr985, Tyr1077, and Tyr1138 with phenylalanine, could induce infertility. This study aimed to describe the reproductive alteration and to explore its mechanism. We compared the reproductive characteristics in the female homozygous (HOM) Y123F mice and wild-type (WT) littermates, analyzing the expression of downstream molecules of LepR, like protein kinase B (Akt)/mammalian target of rapamycin (mTOR), phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and insulin receptor substrate (IRS) in the ovaries. The results showed that 10-week old female Y123F HOM exhibited no reproductive periods, declined anti-mullerian hormone (AMH) levels in the serum and ovaries, reduced primordial follicles, primary follicles, secondary follicles, antral follicles and hardly no corpus lutea (all p < .05). The phosphorylation of downsream Akt, mTOR, S6K1 and eIF4B of LepR were all elevated in the ovaries of the mutated female mice. They also presented a decreased phosphorylation of IRS-1, IRS-2, and PTEN, and a strengthened phosphorylation of FOXO-3A in the ovaries. In conclusions, LepR mutation co...Continue Reading

References

Dec 3, 2003·Trends in Endocrinology and Metabolism : TEM·Sarah H Bates, Martin G Myers
May 7, 2004·Reproduction : the Official Journal of the Society for the Study of Fertility·M MyersJ B Kerr
Jun 10, 2006·The EMBO Journal·David ShahbazianNahum Sonenberg
Nov 19, 2008·Proceedings of the National Academy of Sciences of the United States of America·Lei JiangYong Liu
Apr 23, 2009·Reproduction, Fertility, and Development·Carmen N MirceaRoger A Pierson
Jul 11, 2009·Endocrine Reviews·Deepak Adhikari, Kui Liu
Nov 17, 2009·Trends in Endocrinology and Metabolism : TEM·Pradeep ReddyKui Liu
May 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jing LiAaron J W Hsueh
Sep 15, 2010·Handbook of Experimental Pharmacology·Joanne S Richards, Stephanie A Pangas
Oct 23, 2010·Molecular Cell·Shomit SenguptaDavid M Sabatini
Aug 14, 2012·Cell Metabolism·A Christine Könner, Jens C Brüning
Apr 13, 2013·Frontiers of Medicine·Yingjiang Zhou, Liangyou Rui
Oct 9, 2013·Seminars in Reproductive Medicine·Anne Z Steiner
Oct 19, 2013·Metabolism: Clinical and Experimental·Na WangYu-Cai Fu
Jan 13, 2015·The Journal of Steroid Biochemistry and Molecular Biology·Rui WenJiwen Wang
Aug 3, 2016·Cold Spring Harbor Protocols·Gabriel Gonzalez
Jan 29, 2017·The Journal of Endocrinology·Michael W Pankhurst

❮ Previous
Next ❯

Citations

Mar 17, 2020·Current Pharmaceutical Design·Michail PargianasIoannis P Kosmas
May 1, 2021·International Journal of Molecular Sciences·Karolina WołodkoAntónio Galvão

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.