Skip to main content

Advertisement

Log in

PTEN and Akt expression during growth of human ovarian follicles

  • Physiology
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To assess the expression of PTEN and total and phosphorylated Akt in human ovarian follicles during follicular growth.

Methods

Immunohistochemistry of ovarian tissues and Western blotting and immunofluorescence of primary cultured luteinized granulosa cells for PTEN and Akt.

Results

Immunoreactivity of Akt was found in the oocytes, granulosa cells and theca cells in primordial follicles, follicles at each growing stage and luteal cells. As the follicles grew, staining for PTEN became intense in the granulosa cells, whereas the intensity of phospho-Akt became weak. Western blotting and immunofluorescence analysis using primary cultured granulosa-lutein cells showed Akt and PTEN expression, and phosphorylation of Akt in vitro.

Conclusions

PTEN and Akt are present in the granulosa cells during folliculogenesis. An increase in PTEN may lead to changes in proliferation and/or differentiation of granulosa cells during follicular growth via regulation of Akt phosphorylation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Moor RM, Dai Y, Lee C, Fulka Jr. J. Oocyte maturation and embryonic failure. Hum Reprod Updat 1998;4:223–36.

    Article  CAS  Google Scholar 

  2. Poretsky L, Cataldo NA, Rosenwaks Z, Giudice LC. The insulin-related ovarian regulatory system in health and disease. Endocr Rev 1999;20:535–82.

    Article  PubMed  CAS  Google Scholar 

  3. Bencomo E, Perez R, Arteaga MF, Acosta E, Pena O, Lopez L, et al. Apoptosis of cultured granulosa-lutein cells is reduced by insulin-like growth factor I and may correlate with embryo fragmentation and pregnancy rate. Fertil Steril 2006;85:474–80.

    Article  PubMed  CAS  Google Scholar 

  4. Quirk SM, Cowan RG, Harman RM, Hu CL, Porter DA. Ovarian follicular growth and atresia: the relationship between cell proliferation and survival. J Anim Sci 2004;82(E-Suppl):E40–52.

    PubMed  Google Scholar 

  5. Guthrie HD, Garrett WM, Cooper BS. Follicle-stimulating hormone and insulin-like growth factor-I attenuate apoptosis in cultured porcine granulosa cells. Biol Reprod 1998;58:390–6.

    Article  PubMed  CAS  Google Scholar 

  6. Johnson AL, Bridgham JT, Swenson JA. Activation of the Akt/protein kinase B signaling pathway is associated with granulosa cell survival. Biol Reprod 2001;64:1566–74.

    Article  PubMed  CAS  Google Scholar 

  7. Roberts Jr. CT. Control of insulin-like growth factor (IGF) action by regulation of IGF-I receptor expression. Endocr J 1996;43(Suppl):S49–55.

    PubMed  CAS  Google Scholar 

  8. Cantley LC, Neel BG. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci U S A 1999;96:4240–5.

    Article  PubMed  CAS  Google Scholar 

  9. Kulik G, Klippel A, Weber MJ. Antiapoptotic signalling by the insulin-like growth factor I receptor, phosphatidylinositol 3-kinase, and Akt. Mol Cell Biol 1997;17:1595–606.

    PubMed  CAS  Google Scholar 

  10. Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, et al. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 1997;91:231–41.

    Article  PubMed  CAS  Google Scholar 

  11. Sumitomo M, Iwase A, Zheng R, Navarro D, Kaminetzky D, Shen R, et al. Synergy in tumor suppression by direct interaction of neutral endopeptidase with PTEN. Cancer Cell 2004;5:67–78.

    Article  PubMed  CAS  Google Scholar 

  12. Hu CL, Cowan RG, Harman RM, Quirk SM. Cell cycle progression and activation of Akt kinase are required for insulin-like growth factor I-mediated suppression of apoptosis in granulosa cells. Mol Endocrinol 2004;18:326–38.

    Article  PubMed  CAS  Google Scholar 

  13. Westfall SD, Hendry IR, Obholz KL, Rueda BR, Davis JS. Putative role of the phosphatidylinositol 3-kinase-Akt signaling pathway in the survival of granulosa cells. Endocrine 2000;12:315–21.

    Article  PubMed  CAS  Google Scholar 

  14. Maehama T, Dixon JE. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 1998;273:13375–8.

    Article  PubMed  CAS  Google Scholar 

  15. Leslie NR, Downes CP. PTEN function: how normal cells control it and tumour cells lose it. Biochem J 2004;382:1–11.

    Article  PubMed  CAS  Google Scholar 

  16. Anderson GP, Bozinovski S. Acquired somatic mutations in the molecular pathogenesis of COPD. Trends Pharmacol Sci 2003;24:71–6.

    Article  PubMed  CAS  Google Scholar 

  17. White ES, Thannickal VJ, Carskadon SL, Dickie EG, Livant DL, Markwart S, et al. Integrin alpha4beta1 regulates migration across basement membranes by lung fibroblasts: a role for phosphatase and tensin homologue deleted on chromosome 10. Am J Respir Crit Care Med 2003;168:436–42.

    Article  PubMed  Google Scholar 

  18. Gericke A, Munson M, Ross AH. Regulation of the PTEN phosphatase. Gene 2006;374:1–9.

    Article  PubMed  CAS  Google Scholar 

  19. Harata T, Ando H, Iwase A, Nagasaka T, Mizutani S, Kikkawa F. Localization of angiotensin II, the AT1 receptor, angiotensin-converting enzyme, aminopeptidase A, adipocyte-derived leucine aminopeptidase, and vascular endothelial growth factor in the human ovary throughout the menstrual cycle. Fertil Steril 2006;86:433–9.

    Article  PubMed  Google Scholar 

  20. Monniaux D, Pisselet C. Control of proliferation and differentiation of ovine granulosa cells by insulin-like growth factor-I and follicle-stimulating hormone in vitro. Biol Reprod 1992;46:109–19.

    Article  PubMed  CAS  Google Scholar 

  21. Di Cristofano A, Kotsi P, Peng YF, Cordon-Cardo C, Elkon KB, Pandolfi PP. Impaired Fas response and autoimmunity in Pten +/− mice. Science 1999;285:2122–5.

    Article  PubMed  Google Scholar 

  22. Weng LP, Brown JL, Eng C. PTEN coordinates G(1) arrest by down-regulating cyclin D1 via its protein phosphatase activity and up-regulating p27 via its lipid phosphatase activity in a breast cancer model. Hum Mol Genet 2001;10:599–604.

    Article  PubMed  CAS  Google Scholar 

  23. Dupont J, Renou JP, Shani M, Hennighausen L, LeRoith D. PTEN overexpression suppresses proliferation and differentiation and enhances apoptosis of the mouse mammary epithelium. J Clin Invest 2002;110:815–25.

    Article  PubMed  CAS  Google Scholar 

  24. Zhao H, Dupont J, Yakar S, Karas M, LeRoith D. PTEN inhibits cell proliferation and induces apoptosis by downregulating cell surface IGF-IR expression in prostate cancer cells. Oncogene 2004;23:786–94.

    Article  PubMed  CAS  Google Scholar 

  25. Richards JS, Russell DL, Ochsner S, Hsieh M, Doyle KH, Falender AE, et al. Novel signaling pathways that control ovarian follicular development, ovulation, and luteinization. Recent Prog Horm Res 2002;57:195–220.

    Article  PubMed  CAS  Google Scholar 

  26. Froment P, Bontoux M, Pisselet C, Monget P, Dupont J. PTEN expression in ovine granulosa cells increases during terminal follicular growth. FEBS Lett 2005;579:2376–82.

    Article  PubMed  CAS  Google Scholar 

  27. Mutter GL, Lin MC, Fitzgerald JT, Kum JB, Eng C. Changes in endometrial PTEN expression throughout the human menstrual cycle. J Clin Endocrinol Metab 2000;85:2334–8.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Akira Iwase.

Additional information

Capsule

An increase in PTEN expression of human ovaries may lead to regulation of proliferation and differentation of granulosa cell via a decrease in phosphorylated Akt.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Goto, M., Iwase, A., Ando, H. et al. PTEN and Akt expression during growth of human ovarian follicles. J Assist Reprod Genet 24, 541–546 (2007). https://doi.org/10.1007/s10815-007-9156-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-007-9156-3

Keywords

Navigation