Dataset Information

Regulation of Androgen Receptor Expression Alters AMPK Phosphorylation in the Endometrium: In Vivo and In Vitro Studies in Women with Polycystic Ovary Syndrome.

ABSTRACT: The failure of reproductive success in polycystic ovary syndrome (PCOS) patients could be in part due to endometrial dysfunction. However, no studies have investigated any causality between androgen, androgen receptor (AR) expression, and adenosine monophosphate activated protein kinase (AMPK) activation in the endometrium under physiological and pathological conditions. In the present study, we show that 1) endometrial AR expression levels fluctuate in non-PCOS and PCOS patients during the menstrual cycle; 2) the menstrual phase-dependent alteration of p-AMPK? expression occurs in non-PCOS patients but not in PCOS patients; 3) AR expression is higher in PCOS patients than non-PCOS patients during hyperplasia while AMPK? activation (indicated by the ratio of p-AMPK? to AMPK?); and 4) co-localization of AR and Ki-67 in epithelial cell nuclei is observed in endometrial hyperplasia. Importantly, using in vitro human tissue culture and an in vivo 5?-dihydrotestosterone-treated rat model, we show that the action of androgen on AMPK? activation is likely mediated through nuclear AR, especially in epithelial cells. Collectively, we present evidence that AR expression and AMPK? activation depend on menstrual cycle phase and the presence of PCOS, and the data suggest that AR-mediated regulation of AMPK? activation might play a role in the development of endometrial hyperplasia.

SUBMITTER: Li X

PROVIDER: S-EPMC4671995 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Regulation of Androgen Receptor Expression Alters AMPK Phosphorylation in the Endometrium: In Vivo and In Vitro Studies in Women with Polycystic Ovary Syndrome.

Li Xin X Pishdari Bano B Cui Peng P Hu Min M Yang Hong-Ping HP Guo Yan-Rong YR Jiang Hong-Yuan HY Feng Yi Y Billig Håkan H Shao Ruijin R

International journal of biological sciences 20151101 12

The failure of reproductive success in polycystic ovary syndrome (PCOS) patients could be in part due to endometrial dysfunction. However, no studies have investigated any causality between androgen, androgen receptor (AR) expression, and adenosine monophosphate activated protein kinase (AMPK) activation in the endometrium under physiological and pathological conditions. In the present study, we show that 1) endometrial AR expression levels fluctuate in non-PCOS and PCOS patients during the mens ...[more]

PMID: 26681917

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Project description:ObjectiveWe aimed to study the relationship between ferroptosis proteins and reproductive outcomes of infertile patients with PCOS and construct the related prognostic model.MethodsThese endometrium samples of the study were collected from 33 women with PCOS and 7 control women with successful pregnancies at the Reproductive Center of Lanzhou University Second Hospital, September 2019 to September 2020. The 40 patients' endometrium was identified the differentially expressed proteins (DEPs) using liquid chromatography tandem mass spectrometry. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Ontology (GO) showed that the DEPs related pathways and functions between PCOS and controls. Subsequently, univariate Cox regression analysis and Lasso regression were used to identifying independent prognostic ferroptosis proteins, which were utilized to establish a prognostic model. Then the performance of the prognostic model was evaluated by receiver operating characteristic curve (ROC) and decision curve analysis (DCA). Then clinical data and prognostic model were used to predict the reproductive outcomes of PCOS patients by constructing the nomograms. Finally, we performed the single sample gene set enrichment analysis (ssGSEA) to explore the correlation between risk scores and immune status.ResultsA total of 5331 proteins were identified, 391 proteins were differentially expressed in the PCOS and controls. The KEGG analysis revealed that the ferroptosis pathway was significantly different between PCOS and controls. 5 ferroptosis proteins (GPX4, DPP4, G6PD, PCBP1, and PCBP2) prognostic model (FerSig) was constructed via Cox regression and Lasso regression. Patients were separated into high and low-risk groups according to the FerSig. Kaplan-Meier curve showed that patients in the low-risk group had much better reproductive outcomes than those in the high-risk group. The DCA showed that the risk score was an independent predictive factor for reproductive outcomes. Compared with clinical data, ROC curve analysis indicated the FerSig proteins as a potential diagnostic and prognostic factor in PCOS patients. Functional analysis revealed that the FerSig proteins and immune microenvironment were correlated to the prognosis of PCOS.ConclusionThe prognostic model focused on the FerSig proteins could predict the reproductive outcomes of PCOS patients with decreased endometrial receptivity, and provided theoretical basis for individualized treatment.

Project description:The roles of dietary macronutrients and physical activity (PA) in patients with PCOS have not been sufficiently reported, especially in adolescent girls. To address this knowledge gap, we evaluated the associations between serum concentrations of total testosterone (tT), free testosterone (fT), androstenedione (A), dehydroepiandrosterone-sulfate (DHEA-S), sex hormone-binding globulin (SHBG) and dietary macronutrients intake as well as different types and levels of PA. The study population consisted of 96 girls of Caucasian ancestry, aged 14-18 years: 61 participants with polycystic ovary syndrome (PCOS) and 35 healthy controls. Serum tT, fT, A, DHEA-S, and SHBG were determined in fasting blood. Macronutrient intake and PA levels were assessed by using the three-day food record method and the Beliefs and Eating Habits Questionnaire (KomPAN), respectively. We found several positive correlations between dietary macronutrients such as total fat, saturated fatty acids (SFA), monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA), and hormonal parameters across the entire cohort and in healthy girls. A positive correlation between SHBG and total protein consumption as well as an inverse correlation between SHBG and carbohydrate intake could be determined. No correlation between androgens and macronutrients was found in the PCOS group. In contrast, we observed an inverse correlation between androgen concentrations (except of DHEA-S) and "work/school" and/or "leisure time" PA only in PCOS patients. Moreover, the hormone levels differed according to PA intensity. In conclusion, the impact of diet and PA was strikingly different in adolescents with and without PCOS. These findings indicate that disturbed hormonal homeostasis in PCOS, at least in the youngest patients, likely "overtrump" dietary influences, and otherwise, PA offers a therapeutic potential that requires further evaluation of the long-term effects in randomized studies. (ClinicalTrial.gov Identifier: NCT04738409.).

Dataset Information

Regulation of Androgen Receptor Expression Alters AMPK Phosphorylation in the Endometrium: In Vivo and In Vitro Studies in Women with Polycystic Ovary Syndrome.

Publications

Regulation of Androgen Receptor Expression Alters AMPK Phosphorylation in the Endometrium: In Vivo and In Vitro Studies in Women with Polycystic Ovary Syndrome.

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