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.
Similar content being viewed by others
References
Moor RM, Dai Y, Lee C, Fulka Jr. J. Oocyte maturation and embryonic failure. Hum Reprod Updat 1998;4:223–36.
Poretsky L, Cataldo NA, Rosenwaks Z, Giudice LC. The insulin-related ovarian regulatory system in health and disease. Endocr Rev 1999;20:535–82.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Leslie NR, Downes CP. PTEN function: how normal cells control it and tumour cells lose it. Biochem J 2004;382:1–11.
Anderson GP, Bozinovski S. Acquired somatic mutations in the molecular pathogenesis of COPD. Trends Pharmacol Sci 2003;24:71–6.
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.
Gericke A, Munson M, Ross AH. Regulation of the PTEN phosphatase. Gene 2006;374:1–9.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Author information
Authors and Affiliations
Corresponding author
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
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10815-007-9156-3