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Archives of Gynecology and Obstetrics

Erschienen in:

07.03.2017 | Gynecologic Endocrinology and Reproductive Medicine

Expression of AKT1 along with AKT2 in granulosa-lutein cells of hyperandrogenic PCOS patients

Erschienen in: Archives of Gynecology and Obstetrics | Ausgabe 4/2017

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Abstract

Purpose

AKTs have a pivotal role in the granulosa-lutein cell (GC) proliferation and folliculogenesis, and there is a reciprocal feedback between AKT with androgen. Therefore, we aimed to evaluate the role of AKTs in GCs of hyperandrogenic (+HA) PCOS cases.

Method

There were three groups: control, +HA PCOS and –HA (non-hyperandrogenic) PCOS. All groups were subjected to GnRH antagonist protocol for stimulation of ovulation. Follicular fluid was aspirated from large follicles, and GCs were isolated using cell strainer method. AKT1, AKT2, AKT3, and androgen receptor (AR) mRNA expressions were analyzed with quantitative real-time PCR (qRT-PCR), and total-AKT and p-AKT (Ser⁴⁷³ & Thr³⁰⁸) were investigated using western blotting.

Results

There were high levels of AKT1, AKT2, and AR mRNA expressions and high levels of p-AKT protein expression in the +HA PCOS group (p ≤ 0.05). There was a direct positive correlation between free testosterone (FT) and total testosterone (TT) with the levels of AKT1, AKT2, and p-AKT (Ser⁴⁷³), and also between FT with the levels of AR.

Conclusion

High expressions of AKT1 and AKT2 through possible relation with androgen may cause GCs dysfunction in the +HA PCOS patients.

Głuszak O, Stopińska-Głuszak U, Glinicki P, Kapuścińska R, Snochowska H, Zgliczyński W, Dębski R (2012) Phenotype and metabolic disorders in polycystic ovary syndrome. ISRN Endocrinol 2012. doi:10.5402/2012/569862

Trivax B, Azziz R (2007) Diagnosis of polycystic ovary syndrome. Clin Obstet Gynecol 50(1):168–177CrossRefPubMed

Trikudanathan S (2015) Polycystic ovarian syndrome. Med Clin North Am 99(1):221–235CrossRefPubMed

Chang RJ, Cook-Andersen H (2013) Disordered follicle development. Mol Cell Endocrinol 373(1):51–60CrossRefPubMed

Qu F, Wang F-F, Lu X-E, Dong M-Y, Sheng J-Z, Lv P-P, Ding G-L, Shi B-W, Zhang D, Huang H-F (2010) Altered aquaporin expression in women with polycystic ovary syndrome: hyperandrogenism in follicular fluid inhibits aquaporin-9 in granulosa cells through the phosphatidylinositol 3-kinase pathway. Hum Reprod 25(6):1441–1450CrossRefPubMed

Sir-Petermann T, Codner E, Maliqueo M, Echiburú B, Hitschfeld C, Crisosto N, Pérez-Bravo F, Recabarren SE, Cassorla F (2006) Increased anti-Mullerian hormone serum concentrations in prepubertal daughters of women with polycystic ovary syndrome. J Clin Endocrinol Metab 91(8):3105–3109CrossRefPubMed

Jonard S, Dewailly D (2004) The follicular excess in polycystic ovaries, due to intra-ovarian hyperandrogenism, may be the main culprit for the follicular arrest. Hum Reprod Update 10(2):107–117CrossRefPubMed

Homburg R (2009) Androgen circle of polycystic ovary syndrome. Hum Reprod 24(7):1548–1555CrossRefPubMed

Barth JH, Field HP, Yasmin E, Balen AH (2010) Defining hyperandrogenism in polycystic ovary syndrome: measurement of testosterone and androstenedione by liquid chromatography–tandem mass spectrometry and analysis by receiver operator characteristic plots. Eur J Endocrinol 162(3):611–615CrossRefPubMed

10.

Wang F, Pan J, Liu Y, Meng Q, Lv P, Qu F, Ding G-L, Klausen C, Leung PC, Chan HC (2015) Alternative splicing of the androgen receptor in polycystic ovary syndrome. Proc Natl Acad Sci USA 112(15):4743–4748CrossRefPubMedPubMedCentral

11.

Yang J-L, Zhang C-P, Li L, Huang L, Ji S-Y, Lu C-L, Fan C-H, Cai H, Ren Y, Hu Z-Y (2010) Testosterone induces redistribution of forkhead box-3a and down-regulation of growth and differentiation factor 9 messenger ribonucleic acid expression at early stage of mouse folliculogenesis. Endocrinology 151(2):774–782CrossRefPubMed

12.

Chan TO, Rittenhouse SE, Tsichlis PN (1999) AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide-dependent phosphorylation. Annu Rev Biochem 68(1):965–1014CrossRefPubMed

13.

Makker A, Goel MM, Mahdi AA (2014) PI3K/PTEN/Akt and TSC/mTOR signaling pathways, ovarian dysfunction, and infertility: an update. J Mol Endocrinol 53(3):R103–R118CrossRefPubMed

14.

Goodarzi MO, Jones MR, Chen Y-DI, Azziz R (2008) First evidence of genetic association between AKT2 and polycystic ovary syndrome. Diabetes Care 31(12):2284–2287CrossRefPubMedPubMedCentral

15.

Masure S, Haefner B, Wesselink JJ, Hoefnagel E, Mortier E, Verhasselt P, Tuytelaars A, Gordon R, Richardson A (1999) Molecular cloning, expression and characterization of the human serine/threonine kinase Akt-3. Eur J Biochem 265(1):353–360CrossRefPubMed

16.

Cecconi S, Mauro A, Cellini V, Patacchiola F (2013) The role of Akt signalling in the mammalian ovary. Int J Dev Biol 56(10–12):809–817

17.

Bitting RL, Armstrong AJ (2013) Targeting the PI3K/Akt/mTOR pathway in castration-resistant prostate cancer. Endocr Relat Cancer 20(3):R83–R99CrossRefPubMed

18.

Manin M, Baron S, Goossens K, Beaudoin C, Claude J, Veyssiere G, Verhoeven G, Morel L (2002) Androgen receptor expression is regulated by the phosphoinositide 3-kinase/Akt pathway in normal and tumoral epithelial cells. Biochem J 366(3):729–736CrossRefPubMedPubMedCentral

19.

Kim JJ, Choi YM, Hong MA, Hwang SS, Yoon SH, Chae SJ, Jee BC, Ku SY, Kim JG, Moon SY (2009) Phosphatidylinositol 3-kinase p85α regulatory subunit gene Met326Ile polymorphism in women with polycystic ovary syndrome. Hum Reprod 24(5):1184–1190CrossRefPubMed

20.

Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 81(1):19–25

21.

Dewailly D, Alebić MŠ, Duhamel A, Stojanović N (2014) Using cluster analysis to identify a homogeneous subpopulation of women with polycystic ovarian morphology in a population of non-hyperandrogenic women with regular menstrual cycles. Hum Reprod 29(11):2536–2543CrossRefPubMed

22.

Aghahosseini M, Aleyasin A, Yekehtaz H, Kashani L (2014) Low-dose human chorionic gonadotropin adjunct to an antagonist protocol in assisted reproductive technology: a Randomized Trial Study. Acta Med Iran 52(6):430–437PubMed

23.

Hohmann FP, Macklon NS, Fauser BC (2003) A randomized comparison of two ovarian stimulation protocols with gonadotropin-releasing hormone (GnRH) antagonist cotreatment for in vitro fertilization commencing recombinant follicle-stimulating hormone on cycle day 2 or 5 with the standard long GnRH agonist protocol. J Clin Endocrinol Metab 88(1):166–173CrossRefPubMed

24.

Smith LP, Nierstenhoefer M, Yoo SW, Penzias AS, Tobiasch E, Usheva A (2009) The bile acid synthesis pathway is present and functional in the human ovary. PloS One 4(10):e7333CrossRefPubMedPubMedCentral

25.

Catteau-Jonard S, Jamin SP, Leclerc A, Gonzalès J, Dewailly D, di Clemente N (2008) Anti-Mullerian hormone, its receptor, FSH receptor, and androgen receptor genes are overexpressed by granulosa cells from stimulated follicles in women with polycystic ovary syndrome. J Clin Endocrinol Metab 93(11):4456–4461CrossRefPubMed

26.

Ferrero H, Delgado-Rosas F, Garcia-Pascual CM, Monterde M, Zimmermann RC, Simón C, Pellicer A, Gómez R (2012) Efficiency and purity provided by the existing methods for the isolation of luteinized granulosa cells: a comparative study. Hum Reprod 27(6):1781–1789CrossRefPubMed

27.

Mikaeili S, Rashidi BH, Safa M, Najafi A, Sobhani A, Asadi E, Abbasi M (2016) Altered FoxO3 expression and apoptosis in granulosa cells of women with polycystic ovary syndrome. Arch Gynecol Obstet 294(1):185–192CrossRefPubMed

28.

Dumont A, Robin G, Catteau-Jonard S, Dewailly D (2015) Role of Anti-Müllerian hormone in pathophysiology, diagnosis and treatment of polycystic ovary syndrome: a review. Reprod Biol Endocrinol 13(1):1CrossRef

29.

Cho L, Kilpatrick E, Jayagopal V, Diver M, Atkin S (2008) Biological variation of total testosterone, free androgen index and bioavailable testosterone in polycystic ovarian syndrome: implications for identifying hyperandrogenaemia. Clin Endocrinol (Oxf) 68(3):390–394

30.

Rosenfield RL, Ehrmann DA (2016) The pathogenesis of polycystic ovary syndrome (PCOS). Endocr Rev 37(5):467–520CrossRefPubMed

31.

Li T, Mo H, Chen W, Li L, Xiao Y, Zhang J, Li X, Lu Y (2016) Role of the PI3K-Akt signaling pathway in the pathogenesis of polycystic ovary syndrome. Reprod Sci doi:10.1177/1933719116667606 (epub ahead of print)

32.

Lin SL, Yan LY, Liang XW, Wang ZB, Wang ZY, Qiao J, Schatten H, Sun QY (2009) A novel variant of ER-alpha, ER-alpha36 mediates testosterone-stimulated ERK and Akt activation in endometrial cancer Hec1A cells. Reprod Biol Endocrinol 7(1):1. doi:10.1186/1477-7827-7-102 CrossRef

33.

Goto M, Iwase A, Ando H, Kurotsuchi S, Harata T, Kikkawa F (2007) PTEN and Akt expression during growth of human ovarian follicles. J Assist Reprod Genet 24(11):541–546CrossRefPubMedPubMedCentral

34.

Makker A, Goel MM, Das V, Agarwal A (2012) PI3K-Akt-mTOR and MAPK signaling pathways in polycystic ovarian syndrome, uterine leiomyomas and endometriosis: an update. Gynecol Endocrinol 28(3):175–181CrossRefPubMed

35.

Wuerkenbieke D, Wang J, Li Y, Ma C (2015) miRNA-150 downregulation promotes pertuzumab resistance in ovarian cancer cells via AKT activation. Arch Gynecol Obstet 292(5):1109–1116CrossRefPubMed

36.

Hua G, He C, Lv X, Fan L, Wang C, Remmenga S, Rodabaugh K, Yang L, Lele S, Yang P (2016) The four and a half LIM domains 2 (FHL2) regulates ovarian granulosa cell tumor progression via controlling AKT1 transcription. Cell Death Dis 7(7):e2297. doi:10.1038/cddis.2016.207 CrossRefPubMedPubMedCentral

37.

Restuccia DF, Hynx D, Hemmings BA (2012) Loss of PKBβ/Akt2 predisposes mice to ovarian cyst formation and increases the severity of polycystic ovary formation in vivo. Dis Model Mech 5(3):403–411CrossRefPubMedPubMedCentral

38.

Sarbassov DD, Guertin DA, Ali SM, Sabatini DM (2005) Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307(5712):1098–1101CrossRefPubMed

39.

Bremer AA, Miller WL (2008) The serine phosphorylation hypothesis of polycystic ovary syndrome: a unifying mechanism for hyperandrogenemia and insulin resistance. Fertil Steril 89(5):1039–1048CrossRefPubMed

Titel: Expression of AKT1 along with AKT2 in granulosa-lutein cells of hyperandrogenic PCOS patients
Publikationsdatum: 07.03.2017
Erschienen in: Archives of Gynecology and Obstetrics / Ausgabe 4/2017
Print ISSN: 0932-0067
Elektronische ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-017-4317-9

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Expression of AKT1 along with AKT2 in granulosa-lutein cells of hyperandrogenic PCOS patients

Abstract

Purpose

Method

Results

Conclusion

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