G Protein-Coupled Estrogen Receptor (GPER) Expression in Normal and Abnormal Endometrium

article OA: bronze CC0 ⤵ 45 in-corpus citations
AI-generated summary by claude@2026-06+body, 2026-06-07

Normal endometrium exhibits cyclic GPER expression regulated by estrogen and progesterone receptors, while endometriosis patients show dysregulated GPER overexpression.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

AI-generated deep summary by claude@2026-06, 2026-06-07 · read from full text

This paper investigated whether the membrane G protein-coupled estrogen receptor (GPER/GPR30) shows cyclic expression in endometrium and whether its expression is dysregulated in women with endometriosis. Using real-time RT-PCR and immunohistochemistry in normal endometrium across the menstrual cycle, the authors found cycle-regulated GPER expression with maximal levels in the proliferative phase, and they reported higher GPER expression in eutopic and ectopic endometrium from women with endometriosis compared with normal participants. In Ishikawa endometrial cells, GPER expression increased after estrogen or an ESR1 agonist (but not after a GPER-specific agonist) and decreased after stable progesterone receptor A transfection. A major limitation is that mechanistic regulation was assessed largely through cell-line manipulations rather than direct demonstration of in vivo signaling pathways. This paper is centrally about endometriosis — it reports dysregulated GPER overexpression in eutopic and ectopic endometrium from women with endometriosis and links this to cyclic regulation by nuclear estrogen and progesterone receptors.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Full text 10,877 characters · extracted from oa-doi-fallback · 2 sections · click to expand

Abstract

Rapid estrogen effects are mediated by membrane receptors, and evidence suggests a role for both a membrane-associated form of estrogen receptor alpha (ESR1; ERα) and G-protein coupled receptor 30 (GPER; GPR30). Considering estrogen’s importance in endometrial physiology and endometriosis pathophysiology, we hypothesized that GPER could be involved in both cyclic changes in endometrial estrogen action and that aberrant expression might be seen in the eutopic endometrium of women with endometriosis. Using real-time reverse transcriptase–polymerase chain reaction (RT-PCR) and immunohistochemical analysis of normal endometrium, endometrial samples demonstrated cycle-regulated expression of GPER, with maximal expression in the proliferative phase. Eutopic and ectopic endometrium from women with endometriosis overexpressed GPER as compared to eutopic endometrium of normal participants. Ishikawa cells, an adenocarcinoma cell line, expressed GPER, with increased expression upon treatment with estrogen or an ESR1 agonist, but not with a GPER-specific agonist. Decreased expression was seen in Ishikawa cells stably transfected with progesterone receptor A. Together, these data suggest that normal endometrial GPER expression is cyclic and regulated by nuclear estrogen and progesterone receptors, while expression is dysregulated in endometriosis. Similar content being viewed by others

References

Jensen EV, Desombre ER, Hurst DJ, Kawashima T, Jungblut PW. Estrogen-receptor interactions in target tissues. Arch Anat Microsc Morphol Exp. 1967;56(3):547–569 Mosselman S, Polman J, Dijkema R. ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett. 1996;392(1):49–53 Jensen EV, Jacobson HI. Basic guides to the mechanism of estrgen action. Recent Prog Horm Res. 1962;18:387 Gorski J, Toft D, Shyamala G, Smith D, Notides A. Hormone receptors: studies on the interaction of estrogen with the uterus. Rec Prog Horm Res. 1968;29:45 Falkenstein E, Tillmann HC, Christ M, Feuring M, Wehling M. Multiple actions of steroid hormones—a focus on rapid, nongenomic effects. Pharmacol Rev. 2000;52(4):513–556 Pedram A, Razandi M, Levin ER. Nature of functional estrogen receptors at the plasma membrane. Mol Endocrinol. 2006;20(9):1996–2009 Revankar CM, Cimino DF, Sklar LA, Arterburn JB, Prossnitz ER. A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science. 2005;307(5715):1625–1630 Bologa CG, Revankar CM, Young SM, et al. Virtual and biomolecular screening converge on a selective agonist for GPR30. Nat Chem Biol. 2006;2(4):207–212 Dennis MK, Burai R, Ramesh C, et al. In vivo effects of a GPR30 antagonist. Nat Chem Biol. 2009;5(6):421–427 Hazell G, Yao S, Roper J, Prossnitz E, O’Carroll AM, Lolait S. Localisation of GPR30, a novel G protein-coupled oestrogen receptor, suggests multiple functions in rodent brain and periph eral tissues. J Endocrinol. 2009;202(2):223–236 Haas E, Meyer MR, Schurr U, et al. Differential effects of 17betaestradiol on function and expression of estrogen receptor alpha, estrogen receptor beta, and GPR30 in arteries and veins of patients with atherosclerosis. Hypertension. 2007;49(6):1358–1363 Wang C, Prossnitz ER, Roy SK. Expression of G protein-coupled receptor 30 in the hamster ovary: differential regulation by gonadotropins and steroid hormones. Endocrinology. 2007;148(10):4853–4864 Carmeci C, Thompson DA, Ring HZ, Francke U, Weigel R. Identification of a gene (GPR30) with homology to the G-protein-coupled receptor superfamily associated with estrogen receptor expression in breast cancer. Genomics. 1997;45(3):607–617 Smith HO, Leslie KK, Singh M, et al. GPR30: a novel indicator of poor survival for endometrial carcinoma. Am J Obstet Gynecol. 2007;196(4):386 e1–e9; discussion e9–e11 He YY, Cai B, Yang YX, Liu XL, Wan XP. Estrogenic G proteincoupled receptor 30 signaling is involved in regulation of endometrial carcinoma by promoting proliferation, invasion potential, and interleukin-6 secretion via the MEK/ERK mitogen-activated protein kinase pathway. Cancer Sci. 2009;100(6):1051–1061 Huang GS, Gunter MJ, Arend RC, et al. Co-expression of GPR30 and ERbeta and their association with disease progression in uterine carcinosarcoma. Am J Obstet Gynecol. 2010;203(3):242. e1–e5 Vivacqua A, Bonofiglio D, Recchia AG, et al. The G proteincoupled receptor GPR30 mediates the proliferative effects induced by 17beta-estradiol and hydroxytamoxifen in endometrial cancer cells. Mol Endocrinol. 2006;20(3):631–646 Filardo EJ, Quinn JA, Sabo E. Association of the membrane estrogen receptor, GPR30, with breast tumor metastasis and transactivation of the epidermal growth factor receptor. Steroids. 2008;73(9–10):870–873 Filardo EJ, Quinn JA, Bland KI, Frackelton AR Jr. Estrogeninduced activation of Erk-1 and Erk-2 requires the G proteincoupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HBEGF. Mol Endocrinol. 2000;14(10):1649–1660 Lin BC, Suzawa M, Blind RD, et al. Stimulating the GPR30 estrogen receptor with a novel tamoxifen analogue activates SF-1 and promotes endometrial cell proliferation. Cancer Res. 2009;69(13):5415–5423 Wang A, Ji L, Shang W, et al. Expression of GPR30, ERalpha and ERbeta in endometrium during window of implantation in patients with polycystic ovary syndrome: a pilot study. Gynecol Endocrinol. 2011;27(4):251–255 Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268–279 Noyes R, Hertig A, Rock J. Dating the endometrial biopsy. Fertil Steril. 1950;1:3–25 Irwin JC, de las Fuentes L, Giudice LC. Growth factors and decidualization in vitro. Ann N Y Acad Sci. 1994 Sep 30; 734:7–18. Ryan IP, Schriock ED, Taylor RN. Isolation, characterization, and comparison of human endometrial and endometriosis cells in vitro. J Clin Endocrinol Metab. 1994;78(3):642–649 Li Q, Kannan A, Wang W, et al. Bone morphogenetic protein 2 functions via a conserved signaling pathway involving Wnt4 to regulate uterine decidualization in the mouse and the human. J Biol Chem. 2007;282(43):31725–31732 Ramathal CY, Bagchi IC, Taylor RN, Bagchi MK. Endometrial decidualization: of mice and men. Semin Reprod Med. 2010;28(1):17–26 Stauffer SR, Coletta CJ, Tedesco R, et al. Pyrazole ligands: structure-affinity/activity relationships and estrogen receptor-alpha-selective agonists. J Med Chem. 2000;43(26):4934–4947 Meyers MJ, Sun J, Carlson KE, Marriner GA, Katzenellenbogen BS, Katzenellenbogen JA. Estrogen receptor-beta potency-selective ligands: structure-activity relationship studies of diarylpropionitriles and their acetylene and polar analogues. J Med Chem. 2001;44(24):4230–4251 Smid-Koopman E, Blok LJ, Kuhne LC, et al. Distinct functional differences of human progesterone receptors A and B on gene expression and growth regulation in two endometrial carcinoma cell lines. J Soc Gynecol Investig. 2003;10(1):49–57 Budwit-Novotny DA, McCarty KS, Cox EB, et al. Immuno-histochemical analyses of estrogen receptor in endometrial adenocarcinoma using a monoclonal antibody. Cancer Res. 1986;46(10):5419–5425 Harrington WR, Sheng S, Barnett DH, Petz LN, Katzenellenbogen JA, Katzenellenbogen BS. Activities of estrogen receptor alpha-and beta-selective ligands at diverse estrogen responsive gene sites mediating transactivation or transrepression. Mol Cell Endocrinol. 2003;206(1–2):13–22 Practice Committee of the American Society for Reproductive Medicine. Endometriosis and infertility. Fertil Steril. 2006;86(5 suppl 1):S156–S160 Bulun SE, Cheng YH, Pavone ME, et al. Estrogen receptor-beta, estrogen receptor-alpha, and progesterone resistance in endometriosis. Semin Reprod Med. 2010;28(1):36–43 Bulun SE, Cheng YH, Yin P, et al. Progesterone resistance in endometriosis: link to failure to metabolize estradiol. Mol Cell Endocrinol. 2006;248(1–2):94–103 Burney RO, Talbi S, Hamilton AE, et al. Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis. Endocrinology. 2007;148(8):3814–3826 Fazleabas AT. Progesterone resistance in a baboon model of endometriosis. Semin Reprod Med. 2010;28(1):75–80 Kolkova Z, Noskova V, Ehinger A, Hansson S, Casslen BG. protein-coupled estrogen receptor 1 (GPER, GPR 30) in normal human endometrium and early pregnancy decidua. Mol Hum Reprod. 2010;16(10):743–751 Sanden C, Broselid S, Cornmark L, et al. G protein-coupled estrogen receptor 1/G protein-coupled receptor 30 localizes in the plasma membrane and traffics intracellularly on cytokeratin intermediate filaments. Mol Pharmacol. 2011;79(3):400–410 Lecce G, Meduri G, Ancelin M, Bergeron C, Perrot-Applanat M. Presence of estrogen receptor beta in the human endometrium through the cycle: expression in glandular, stromal, and vascular cells. J Clin Endocrinol Metab. 2001;86(3):1379–1386 Matsuzaki S, Fukaya T, Suzuki T, Murakami T, Sasano H, Yajima A. Oestrogen receptor alpha and beta mRNA expression in human endometrium throughout the menstrual cycle. Mol Hum Reprod. 1999;5(6):559–564 Press MF, Nousek-Goebl N, King WJ, Herbst AL, Greene GL. Immunohistochemical assessment of estrogen receptor distribution in the human endometrium throughout the menstrual cycle. Lab Invest. 1984;51(5):495–503 Mangal RK, Wiehle RD, Poindexter AN 3rd, Weigel NL. Differential expression of uterine progesterone receptor forms A and B during the menstrual cycle. J Steroid Biochem Mol Biol. 1997;63(4–6):195–202 Otto C, Fuchs I, Kauselmann G, et al. GPR30 does not mediate estrogenic responses in reproductive organs in mice. Biol Reprod. 2009;80(1):34–41 Pandey DP, Lappano R, Albanito L, Madeo A, Maggiolini M, Picard D. Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF. EMBO J. 2009;28(5):523–532 Zhang Z, Duan L, Du X, et al. The proliferative effect of estradiol on human prostate stromal cells is mediated through activation of ERK. Prostate. 2008;68(5):508–516 Albanito L, Madeo A, Lappano R, et al. G protein-coupled receptor 30 (GPR30) mediates gene expression changes and growth response to 17beta-estradiol and selective GPR30 ligand G-1 in ovarian cancer cells. Cancer Res. 2007;67(4):1859–1866 Vivacqua A, Bonofiglio D, Albanito L, et al. 17beta-estradiol, genistein, and 4-hydroxytamoxifen induce the proliferation of thyroid cancer cells through the g protein-coupled receptor GPR30. Mol Pharmacol. 2006;70(4):1414–1423 Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Plante, B.J., Lessey, B.A., Taylor, R.N. et al. G Protein-Coupled Estrogen Receptor (GPER) Expression in Normal and Abnormal Endometrium. Reprod. Sci. 19, 684–693 (2012). https://doi.org/10.1177/1933719111431000 Published: Issue date: DOI: https://doi.org/10.1177/1933719111431000

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

mesh:D004715

MeSH descriptors

Endometriosis Endometrium Gene Expression Regulation Menstrual Cycle Receptors, Estrogen Receptors, G-Protein-Coupled Adolescent Adult Cells, Cultured Endometriosis Endometriosis Endometrium Endometrium Endometrium Epithelial Cells Epithelial Cells Epithelial Cells Epithelial Cells Female Humans

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (53)

Cited by (45)

Source provenance

europepmc
last seen: 2026-06-04T01:30:01.192114+00:00
openalex
last seen: 2026-06-04T00:00:01.174412+00:00
pubmed
last seen: 2026-05-13T22:16:17.081435+00:00
License: CC0 · commercial use OK