{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:24:39Z","timestamp":1790753079477,"version":"4.1.0"},"reference-count":68,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T00:00:00Z","timestamp":1700784000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cInstitut National de la Sant\u00e9 &amp; de la Recherche M\u00e9dicale\u201d (Inserm)"},{"name":"\u201cCentre National de la Recherche Scientifique\u201d (CNRS)"},{"name":"Universit\u00e9 Paris Cit\u00e9"},{"name":"Ecole Doctorale Bio-SPC (C. Marie)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Estradiol (E2) is a major hormone-controlling folliculogenesis whose dysfunction may participate in polycystic ovary syndrome (PCOS) infertility. To determine whether both the concentration and action of E2 could be impaired in non-hyperandrogenic overweight PCOS women, we isolated granulosa cells (GCs) and follicular fluid (FF) from follicles of women undergoing ovarian stimulation (27 with PCOS, and 54 without PCOS). An analysis of the transcript abundance of 16 genes in GCs showed that androgen and progesterone receptor expressions were significantly increased in GCs of PCOS (by 2.7-fold and 1.5-fold, respectively), while those of the steroidogenic enzymes CYP11A1 and HSD3B2 were down-regulated (by 56% and 38%, respectively). Remarkably, treatment of GC cultures with E2 revealed its ineffectiveness in regulating the expression of several key endocrine genes (e.g., GREB1 or BCL2) in PCOS. Additionally, a comparison of the steroid concentrations (measured by GC\/MS) in GCs with those in FF of matched follicles demonstrated that the significant decline in the E2 concentration (by 23%) in PCOS FF was not the result of the E2 biosynthesis reduction. Overall, our study provides novel hallmarks of PCOS by highlighting the ineffective E2 signaling in GCs as well as the dysregulation in the expression of genes involved in follicular growth, which may contribute to aberrant folliculogenesis in non-hyperandrogenic women with PCOS.<\/jats:p>","DOI":"10.3390\/ijms242316689","type":"journal-article","created":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T03:43:59Z","timestamp":1700797439000},"page":"16689","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Dysfunction of Human Estrogen Signaling as a Novel Molecular Signature of Polycystic Ovary Syndrome"],"prefix":"10.3390","volume":"24","author":[{"given":"Cl\u00e9mentine","family":"Marie","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, Inserm, Unit\u00e9 de Biologie Fonctionnelle et Adaptative, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Pierre","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, Inserm, Unit\u00e9 de Biologie Fonctionnelle et Adaptative, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Mayeur","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine de la Reproduction et Pr\u00e9servation de la Fertilit\u00e9, H\u00f4pital Antoine B\u00e9cl\u00e8re, 92140 Clamart, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4959-1214","authenticated-orcid":false,"given":"Frank","family":"Giton","sequence":"additional","affiliation":[{"name":"AP-HP, P\u00f4le Biologie-Pathologie Henri Mondor, Inserm IMRB U955, 94010 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Corre","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, Inserm, Unit\u00e9 de Biologie Fonctionnelle et Adaptative, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1549-1802","authenticated-orcid":false,"given":"Micha\u00ebl","family":"Grynberg","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, Inserm, Unit\u00e9 de Biologie Fonctionnelle et Adaptative, 75013 Paris, France"},{"name":"Service de M\u00e9decine de la Reproduction et Pr\u00e9servation de la Fertilit\u00e9, H\u00f4pital Antoine B\u00e9cl\u00e8re, 92140 Clamart, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00eblle","family":"Cohen-Tannoudji","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, Inserm, Unit\u00e9 de Biologie Fonctionnelle et Adaptative, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line J.","family":"Guigon","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, Inserm, Unit\u00e9 de Biologie Fonctionnelle et Adaptative, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8439-1453","authenticated-orcid":false,"given":"St\u00e9phanie","family":"Chauvin","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, CNRS, Inserm, Unit\u00e9 de Biologie Fonctionnelle et Adaptative, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wolf, W.M., Wattick, R.A., Kinkade, O.N., and Olfert, M.D. (2018). Geographical Prevalence of Polycystic Ovary Syndrome as Determined by Region and Race\/Ethnicity. Int. J. Environ. Res. Public Health, 15.","DOI":"10.3390\/ijerph15112589"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1210\/jc.2007-1650","article-title":"Granulosa cell survival and proliferation are altered in polycystic ovary syndrome","volume":"93","author":"Das","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1093\/humupd\/dmn015","article-title":"Follicle dynamics and anovulation in polycystic ovary syndrome","volume":"14","author":"Franks","year":"2008","journal-title":"Hum. Reprod. Update"},{"key":"ref_4","first-page":"3984","article-title":"Premature response to luteinizing hormone of granulosa cells from anovulatory women with polycystic ovary syndrome: Relevance to mechanism of anovulation","volume":"83","author":"Willis","year":"1998","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4418","DOI":"10.1210\/jc.2007-0729","article-title":"Abnormal preantral folliculogenesis in polycystic ovaries is associated with increased granulosa cell division","volume":"92","author":"Stubbs","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4617","DOI":"10.18632\/aging.202421","article-title":"LNK promotes granulosa cell apoptosis in PCOS via negatively regulating insulin-stimulated AKT-FOXO3 pathway","volume":"13","author":"Tan","year":"2021","journal-title":"Aging"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Gong, Y., Luo, S., Fan, P., Zhu, H., Li, Y., and Huang, W. (2020). Growth hormone activates PI3K\/Akt signaling and inhibits ROS accumulation and apoptosis in granulosa cells of patients with polycystic ovary syndrome. Reprod. Biol. Endocrinol., 18.","DOI":"10.1186\/s12958-020-00677-x"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s00404-016-4068-z","article-title":"Altered FoxO3 expression and apoptosis in granulosa cells of women with polycystic ovary syndrome","volume":"294","author":"Mikaeili","year":"2016","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11648","DOI":"10.1038\/s41598-023-38340-1","article-title":"Evaluation of the p53 pathway in polycystic ovarian syndrome pathogenesis and apoptosis enhancement in human granulosa cells through transcriptome data analysis","volume":"13","author":"Zanjirband","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1080\/09513590.2021.1928066","article-title":"PATL2 regulated the apoptosis of ovarian granulosa cells in patients with PCOS","volume":"37","author":"Peng","year":"2021","journal-title":"Gynecol. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1111\/j.1365-2265.1990.tb00879.x","article-title":"Follicular fluid concentrations of insulin-like growth factor 1, epidermal growth factor, transforming growth factor-alpha and sex-steroids in volume matched normal and polycystic human follicles","volume":"32","author":"Eden","year":"1990","journal-title":"Clin. Endocrinol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8218650","DOI":"10.1155\/2019\/8218650","article-title":"Melatonin Reduces Androgen Production and Upregulates Heme Oxygenase-1 Expression in Granulosa Cells from PCOS Patients with Hypoestrogenia and Hyperandrogenia","volume":"2019","author":"Yu","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"187","DOI":"10.4103\/0974-1208.142479","article-title":"Follicular steroid hormones as markers of oocyte quality and oocyte development potential","volume":"7","author":"Carpintero","year":"2014","journal-title":"J. Hum. Reprod. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.fertnstert.2014.11.015","article-title":"Oocyte environment: Follicular fluid and cumulus cells are critical for oocyte health","volume":"103","author":"Dumesic","year":"2015","journal-title":"Fertil. Steril."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1111\/aogs.13805","article-title":"Proteomic analysis of follicular fluid during human ovulation","volume":"99","author":"Zakerkish","year":"2020","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s10815-016-0657-9","article-title":"Exosome-mediated communication in the ovarian follicle","volume":"33","year":"2016","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1051\/rnd:19980401","article-title":"Control of oocyte growth and maturation by follicular cells and molecules present in follicular fluid","volume":"38","author":"Driancourt","year":"1998","journal-title":"A review. Reprod. Nutr. Dev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"110030","DOI":"10.1016\/j.cellsig.2021.110030","article-title":"PCOS follicular fluid derived exosomal miR-424-5p induces granulosa cells senescence by targeting CDCA4 expression","volume":"85","author":"Yuan","year":"2021","journal-title":"Cell Signal"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/s10815-018-1143-3","article-title":"Influence of follicular fluid and cumulus cells on oocyte quality: Clinical implications","volume":"35","author":"Giorgi","year":"2018","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.fertnstert.2011.08.017","article-title":"Serum and follicular fluid ghrelin levels negatively reflect human oocyte quality and in vitro embryo development","volume":"96","author":"Li","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1016\/j.fertnstert.2009.12.081","article-title":"Steroid profiles in ovarian follicular fluid in women with and without polycystic ovary syndrome, analyzed by liquid chromatography-tandem mass spectrometry","volume":"94","author":"Naessen","year":"2010","journal-title":"Fertil. Steril."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Yang, Z., Zhou, W., Zhou, C., Zhou, Y., Liu, X., Ding, G., Hu, Y., Pan, J., Sheng, J., and Jin, L. (2021). Steroid metabolome profiling of follicular fluid in normo- and hyperandrogenic women with polycystic ovary syndrome. J. Steroid Biochem. Mol. Biol., 206.","DOI":"10.1016\/j.jsbmb.2020.105806"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1093\/humrep\/deaa098","article-title":"Significance of pro-angiogenic estrogen metabolites in normal follicular development and follicular growth arrest in polycystic ovary syndrome","volume":"35","author":"Henriquez","year":"2020","journal-title":"Hum. Reprod."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/molehr\/4.1.1","article-title":"Aromatase mRNA expression in individual follicles from polycystic ovaries","volume":"4","author":"Jakimiuk","year":"1998","journal-title":"Mol. Hum. Reprod."},{"key":"ref_25","first-page":"3686","article-title":"A mechanism for the suppression of estrogen production in polycystic ovary syndrome","volume":"81","author":"Agarwal","year":"1996","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Chauvin, S., Cohen-Tannoudji, J., and Guigon, C.J. (2022). Estradiol Signaling at the Heart of Folliculogenesis: Its Potential Deregulation in Human Ovarian Pathologies. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010512"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1111\/j.1600-0684.1990.tb00463.x","article-title":"Role of estradiol in regulating ovarian follicular atresia in rhesus monkeys: A review","volume":"19","author":"Hutz","year":"1990","journal-title":"J. Med. Primatol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Pierre, A., Mayeur, A., Marie, C., Cluzet, V., Chauvin, J., Frydman, N., Grynberg, M., Cohen-Tannoudji, J., Guigon, C.J., and Chauvin, S. (2021). Estradiol Regulates mRNA Levels of Estrogen Receptor Beta 4 and Beta 5 Isoforms and Modulates Human Granulosa Cell Apoptosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22095046"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"16057","DOI":"10.1038\/nrdp.2016.57","article-title":"Polycystic ovary syndrome","volume":"2","author":"Azziz","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"hoaa009","DOI":"10.1093\/hropen\/hoaa009","article-title":"ESHRE guideline: Ovarian stimulation for IVF\/ICSI(dagger)","volume":"2020","author":"Bosch","year":"2020","journal-title":"Hum. Reprod. Open"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1093\/humrep\/deg208","article-title":"Prediction of ovarian hyperstimulation syndrome (OHSS). Estradiol level has an important role in the prediction of OHSS","volume":"18","author":"Aboulghar","year":"2003","journal-title":"Hum. Reprod."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.fertnstert.2005.07.1292","article-title":"Incidence and prediction of ovarian hyperstimulation syndrome in women undergoing gonadotropin-releasing hormone antagonist in vitro fertilization cycles","volume":"85","author":"Papanikolaou","year":"2006","journal-title":"Fertil. Steril."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ciesiolka, S., Budna, J., Jopek, K., Bryja, A., Kranc, W., Chachula, A., Borys, S., Dyszkiewicz Konwinska, M., Ziolkowska, A., and Antosik, P. (2016). Influence of Estradiol-17beta on Progesterone and Estrogen Receptor mRNA Expression in Porcine Follicular Granulosa Cells during Short-Term, In Vitro Real-Time Cell Proliferation. Biomed. Res. Int., 2016.","DOI":"10.1155\/2016\/8431018"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/path.5843","article-title":"Estradiol promotes cell survival and induces Greb1 expression in granulosa cell tumors of the ovary through an ERalpha-dependent mechanism","volume":"256","author":"Cluzet","year":"2022","journal-title":"J. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1095\/biolreprod.105.047407","article-title":"Distinct regulation by steroids of messenger RNAs for FSHR and CYP19A1 in bovine granulosa cells","volume":"75","author":"Luo","year":"2006","journal-title":"Biol. Reprod."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"23652","DOI":"10.18632\/aging.203639","article-title":"Up-regulation of SIRT1 induced by 17beta-estradiol promotes autophagy and inhibits apoptosis in osteoblasts","volume":"13","author":"Wang","year":"2021","journal-title":"Aging"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1007\/s43032-019-00099-0","article-title":"Androgens Modulate Rat Granulosa Cell Steroidogenesis","volume":"27","author":"Doblado","year":"2020","journal-title":"Reprod. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4456","DOI":"10.1210\/jc.2008-1231","article-title":"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","volume":"93","author":"Jamin","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Zhou, R., Li, S., Liu, J., Wu, H., Yao, G., Sun, Y., Chen, Z.J., Li, W., and Du, Y. (2020). Up-regulated FHL2 inhibits ovulation through interacting with androgen receptor and ERK1\/2 in polycystic ovary syndrome. eBioMedicine, 52.","DOI":"10.1016\/j.ebiom.2020.102635"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4743","DOI":"10.1073\/pnas.1418216112","article-title":"Alternative splicing of the androgen receptor in polycystic ovary syndrome","volume":"112","author":"Wang","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Manavathi, B., Samanthapudi, V.S., and Gajulapalli, V.N. (2014). Estrogen receptor coregulators and pioneer factors: The orchestrators of mammary gland cell fate and development. Front. Cell Dev. Biol., 2.","DOI":"10.3389\/fcell.2014.00034"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1093\/humrep\/deq078","article-title":"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","volume":"25","author":"Qu","year":"2010","journal-title":"Hum. Reprod."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1210\/me.2004-0021","article-title":"Transrepression of estrogen receptor beta signaling by nuclear factor-kappab in ovarian granulosa cells","volume":"18","author":"Chu","year":"2004","journal-title":"Mol. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.mce.2019.02.015","article-title":"Expression of genes controlling steroid metabolism and action in granulosa-lutein cells of women with polycystic ovaries","volume":"486","author":"Lerner","year":"2019","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s10815-015-0612-1","article-title":"What maintains the high intra-follicular estradiol concentration in pre-ovulatory follicles?","volume":"33","author":"Bentov","year":"2016","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_46","first-page":"367","article-title":"Proteomic profile of follicular fluid from patients with polycystic ovary syndrome (PCOS) submitted to in vitro fertilization (IVF) compared to oocyte donors","volume":"23","author":"Domingues","year":"2019","journal-title":"JBRA Assist. Reprod."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1210\/jc.2014-2086","article-title":"Proteomics of follicular fluid from women with polycystic ovary syndrome suggests molecular defects in follicular development","volume":"100","author":"Ambekar","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s10815-023-02724-z","article-title":"Molecular characterization of extracellular vesicles derived from follicular fluid of women with and without PCOS: Integrating analysis of differential miRNAs and proteins reveals vital molecules involving in PCOS","volume":"40","author":"Yang","year":"2023","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/jcmm.14642","article-title":"S100-A9 protein in exosomes derived from follicular fluid promotes inflammation via activation of NF-kappaB pathway in polycystic ovary syndrome","volume":"24","author":"Li","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Yu, L., Liu, M., Wang, Z., Liu, T., Liu, S., Wang, B., Pan, B., Dong, X., and Guo, W. (2021). Correlation between steroid levels in follicular fluid and hormone synthesis related substances in its exosomes and embryo quality in patients with polycystic ovary syndrome. Reprod. Biol. Endocrinol., 19.","DOI":"10.1186\/s12958-021-00749-6"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Fedotcheva, T.A., Fedotcheva, N.I., and Shimanovsky, N.L. (2022). Progesterone as an Anti-Inflammatory Drug and Immunomodulator: New Aspects in Hormonal Regulation of the Inflammation. Biomolecules, 12.","DOI":"10.3390\/biom12091299"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1093\/molehr\/gan082","article-title":"Gene expression microarray profiles of cumulus cells in lean and overweight-obese polycystic ovary syndrome patients","volume":"15","author":"Kenigsberg","year":"2009","journal-title":"Mol. Hum. Reprod."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"14994","DOI":"10.1038\/srep14994","article-title":"Functional microarray analysis of differentially expressed genes in granulosa cells from women with polycystic ovary syndrome related to MAPK\/ERK signaling","volume":"5","author":"Lan","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1093\/molehr\/gat051","article-title":"Differential expression of inflammation-related genes in the ovarian stroma and granulosa cells of PCOS women","volume":"20","author":"Schmidt","year":"2014","journal-title":"Mol. Hum. Reprod."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1210\/endo.133.2.8344215","article-title":"Hormonal regulation, localization, and functional activity of the progesterone receptor in granulosa cells of rat preovulatory follicles","volume":"133","author":"Natraj","year":"1993","journal-title":"Endocrinology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1210\/mend-5-7-967","article-title":"Transient expression of progesterone receptor messenger RNA in ovarian granulosa cells after the preovulatory luteinizing hormone surge","volume":"5","author":"Park","year":"1991","journal-title":"Mol. Endocrinol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1365-2265.1980.tb02132.x","article-title":"The polycystic ovary syndrome","volume":"12","author":"Yen","year":"1980","journal-title":"Clin. Endocrinol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1210\/me.2003-0380","article-title":"Coordinate transcription of the ADAMTS-1 gene by luteinizing hormone and progesterone receptor","volume":"18","author":"Doyle","year":"2004","journal-title":"Mol. Endocrinol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1007\/s10815-017-0913-7","article-title":"Follicular ADAMTS-1 and aggrecan levels in polycystic ovary syndrome","volume":"34","author":"Tola","year":"2017","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_60","first-page":"2696","article-title":"Endometrial progesterone receptor isoforms in women with polycystic ovary syndrome","volume":"10","author":"Hu","year":"2018","journal-title":"Am. J. Transl. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1016\/j.biopha.2018.10.128","article-title":"Metformin inhibits estradiol and progesterone-induced decidualization of endometrial stromal cells by regulating expression of progesterone receptor, cytokines and matrix metalloproteinases","volume":"109","author":"Xiong","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Xing, D., Oparil, S., Yu, H., Gong, K., Feng, W., Black, J., Chen, Y.F., and Nozell, S. (2012). Estrogen modulates NFkappaB signaling by enhancing IkappaBalpha levels and blocking p65 binding at the promoters of inflammatory genes via estrogen receptor-beta. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0036890"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3050","DOI":"10.1210\/me.2004-0074","article-title":"Abnormal gene expression profiles in human ovaries from polycystic ovary syndrome patients","volume":"18","author":"Jansen","year":"2004","journal-title":"Mol. Endocrinol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"62","DOI":"10.3389\/fendo.2017.00062","article-title":"Gonadotropin-Inhibitory Hormone Plays Roles in Stress-Induced Reproductive Dysfunction","volume":"8","author":"Iwasa","year":"2017","journal-title":"Front. Endocrinol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1177\/153537020322800201","article-title":"Regulation of signaling protein function and trafficking by the hsp90\/hsp70-based chaperone machinery","volume":"228","author":"Pratt","year":"2003","journal-title":"Exp. Biol. Med."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"De Amicis, F., Chiodo, C., Morelli, C., Casaburi, I., Marsico, S., Bruno, R., Sisci, D., Ando, S., and Lanzino, M. (2019). AIB1 sequestration by androgen receptor inhibits estrogen-dependent cyclin D1 expression in breast cancer cells. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-6262-4"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3970","DOI":"10.1210\/jc.2017-00308","article-title":"Dysregulation of the Anti-Mullerian Hormone System by Steroids in Women with Polycystic Ovary Syndrome","volume":"102","author":"Pierre","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"E292","DOI":"10.1210\/jc.2014-2658","article-title":"Sex steroids, precursors, and metabolite deficiencies in men with isolated hypogonadotropic hypogonadism and panhypopituitarism: A GCMS-based comparative study","volume":"100","author":"Giton","year":"2015","journal-title":"J. Clin. Endocrinol. 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