The role of androst-5-ene-3β,17β-diol (androstenediol) in cell proliferation in endometrium of women with polycystic ovary syndrome

Plaza-Parrochia, Francisca; Bacallao, Ketty; Poblete, Cristian; Gabler, Fernando; Carvajal, Rodrigo; Romero, Carmen; Valladares, Luis; Vega, Margarita

doi:10.1016/j.steroids.2014.07.008

Cited by 19 publications

(34 citation statements)

References 45 publications

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“…With this evidence, the authors concluded that telomerase may be an important driving force in developing PCOS and related phenotypes ( Lee et al ., 2015 ). Considering the suggested role that unopposed estrogen and excessive androgens have on TA ( Boggess et al ., 2006 ; Nourbakhsh et al ., 2010 ) and cellular proliferation in various carcinoma cells including EC cells ( Chao et al ., 2013 ; Dumesic and Lobo, 2013 ; Plaza-Parrochia et al ., 2014 ; Hapangama and Bulmer, 2016 ; Kamal et al ., 2016 ), studies examining the involvement of telomerase in the endometrium of women with PCOS may unravel novel avenues for therapeutic manipulation.…”

Section: The Endometriummentioning

confidence: 99%

Implications of telomeres and telomerase in endometrial pathology

Hapangama

Kamal

Saretzki

2016

Hum. Reprod. Update

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BACKGROUNDEukaryotic chromosomal ends are linear and are protected by nucleoprotein complexes known as telomeres. The complex structural anatomy and the diverse functions of telomeres as well as the unique reverse transcriptase enzyme, telomerase that maintains telomeres are under intensive scientific scrutiny. Both are involved in many human diseases including cancer, but also in ageing and chronic disease such as diabetes. Their intricate involvement in many cellular processes and pathways is being dynamically deciphered in many organs including the endometrium. This review summarizes our current knowledge on the topic of telomeres and telomerase and their potential role in providing plausible explanations for endometrial aberrations related to common gynaecological pathologies.OBJECTIVE AND RATIONALEThis review outlines the recent major findings in telomere and telomerase functions in the context of endometrial biology. It highlights the contemporary discoveries in hormonal regulation, normal endometrial regeneration, stem cells and common gynaecological diseases such as endometriosis, infertility, recurrent reproductive failure and endometrial cancer (EC).SEARCH METHODSThe authors carried out systematic PubMed (Medline) and Ovid searches using the key words: telomerase, telomeres, telomere length, human telomerase reverse transcriptase, telomeric RNA component, with endometrium, hormonal regulation, endometrial stem/progenitor cells, endometrial regeneration, endometriosis, recurrent miscarriage, infertility, endometrial hyperplasia, EC and uterine cancer. Publications used in this review date from 1995 until 31st June 2016.OUTCOMESThe human endometrium is a unique somatic organ, which displays dynamic telomerase activity (TA) related to the menstrual cycle. Telomerase is implicated in almost all endometrial pathologies and appears to be crucial to endometrial stem cells. In particular, it is vital for normal endometrial regeneration, providing a distinct route to formulate possible curative, non-hormonal therapies to treat chronic endometrial conditions. Furthermore, our current understanding of telomere maintenance in EC is incomplete. Data derived from other malignancies on the role of telomerase in carcinogenesis cannot be extrapolated to EC because unlike in other cancers, TA is already present in proliferating healthy endometrial cells.WIDER IMPLICATIONSSince telomerase is pivotal to endometrial regeneration, further studies elucidating the role of telomeres, telomerase, their associated proteins and their regulation in normal endometrial regeneration as well as their role in endometrial pathologies are essential. This approach may allow future development of novel treatment strategies that are not only non-hormonal but also potentially curative.

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Section: The Endometriummentioning

confidence: 99%

Implications of telomeres and telomerase in endometrial pathology

Hapangama

Kamal

Saretzki

2016

Hum. Reprod. Update

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“…In addition, recent results indicate that in endometria of women with PCOS exists a high metabolism of dehydroepiandrosterone to androstenediol 32 and increased concentrations of androstenediol. 15 Androstenediol is structurally an androgen although functions as an estrogen, activating nuclear receptors. 36,37,38 It has been described that androstenediol exhibits similar effects to 17b-estradiol in human endometrial cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…Androstenediol modulates molecules involved in favoring cell cycle progression, which would increase cellular proliferation of endometrial cell lines and tissues. 15 Furthermore, the endocrine status of PCOS, where estrogen action at the endometrial level is enhanced, 13,14 could induce a deregulation of the cellular cycle in endometrial cells. 9,39 The mechanism by which increased ERa phosphorylation at Ser118 could be activated is through the binding of the ligand.…”

Section: Discussionmentioning

confidence: 99%

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Levels of Regulatory Proteins Associated With Cell Proliferation in Endometria From Untreated Patients Having Polycystic Ovarian Syndrome With and Without Endometrial Hyperplasia

et al. 2016

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Polycystic ovarian syndrome (PCOS) has been associated with endometrial hyperplasia and cancer. The aim of this study was to establish whether the expression of proliferation regulatory proteins in the endometria of patients having PCOS, with or without hyperplasia, differs from control women. Control endometria (CE), patients having PCOS without and with endometrial hyperplasia (PCOSE and HPCOSE, respectively), and that of women with endometrial hyperplasia (HE) were used. The phosphorylated estrogen receptor form (pERα), similar to mother against decapentaplegic (SMAD) 2, SMAD3, and SMAD4, vascular epithelial growth factor (VEGF), and phosphorylated SMAD (pSMAD) 2 and pSMAD3 were detected by immunohistochemistry or Western blot. The results show higher levels of pERα in HE versus CE (P < .05), while higher VEGF levels were found in PCOSE and HE (P < .05) compared to CE; SMAD2 diminished in HE (P < .05) versus CE. Consequently, the higher levels of VEGF and pERα in PCOSE could represent early changes in the progression of PCOSE toward hyperplasia and cancer, whereas changes observed in SMAD proteins support the differential origin of the pathologies of HPCOSE and HE.

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“…They attributed the higher production of androstenediol to a higher concentration of 17b-HSD, type 1 in PCOS patients, based on one of their previous studies. 19 In a subsequent study, PlazaParrochia et al 20 showed that androstenediol enhances cell proliferation of the endometrium by increasing the levels of cyclin D1 and decreasing those of p27, which are positive and negative regulators of the cell cycle, respectively. However, there are no studies evaluating tissue levels of androstenediol in endometria of women with hyperplasia or adenocarcinoma.…”

mentioning

confidence: 98%

Effect of intravaginal dehydroepiandrosterone treatment on the endometrium

Stanczyk

2015

Menopause

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The role of androst-5-ene-3β,17β-diol (androstenediol) in cell proliferation in endometrium of women with polycystic ovary syndrome

Cited by 19 publications

References 45 publications

Implications of telomeres and telomerase in endometrial pathology

Implications of telomeres and telomerase in endometrial pathology

Levels of Regulatory Proteins Associated With Cell Proliferation in Endometria From Untreated Patients Having Polycystic Ovarian Syndrome With and Without Endometrial Hyperplasia

Effect of intravaginal dehydroepiandrosterone treatment on the endometrium

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