J Menopausal Med.  2015 Aug;21(2):79-81. 10.6118/jmm.2015.21.2.79.

G-protein Coupled Estrogen Receptor (GPER/GPR30) and Women's Health

• Kim MJ
• Kim TH
• Lee HH

• KMID: 2200980
• DOI: http://doi.org/10.6118/jmm.2015.21.2.79

Abstract

Estrogen - the female sexual hormone playing the most important role - plays a physiologically significant role, not only regulating in cell signals with second messenger but also being active in regulating transcription. Estrogen receptor (ER) which is a protein accepting estrogen not only play the role of a transcription factor combining with other genes to regulate their activity like other nuclear receptors but also performs external activities, combining with DNA, etc. G-protein coupled ER (GPER) that has been recently discovered exists as 7-membrane and has non-genomic (rapid) signaling. These functions, however, are not extensively addressed. This paper discusses the roles of GPER and its physiological mechanism.

Keyword

Estradiol; Estrogens; Genomics; GTP-binding proteins

MeSH Terms

DNA
Estradiol
Estrogens*
Female
Genomics
GTP-Binding Proteins*
Humans
Receptors, Cytoplasmic and Nuclear
Second Messenger Systems
Transcription Factors
Women's Health*
DNA
Estradiol
Estrogens
GTP-Binding Proteins
Receptors, Cytoplasmic and Nuclear
Transcription Factors

Reference

1. Prossnitz ER, Barton M. The G-protein-coupled estrogen receptor GPER in health and disease. Nat Rev Endocrinol. 2011; 7:715–726.

2. Kolkova Z, Noskova V, Ehinger A, Hansson S, Casslén B. G protein-coupled estrogen receptor 1 (GPER, GPR 30) in normal human endometrium and early pregnancy decidua. Mol Hum Reprod. 2010; 16:743–751.

3. Owman C, Blay P, Nilsson C, Lolait SJ. Cloning of human cDNA encoding a novel heptahelix receptor expressed in Burkitt's lymphoma and widely distributed in brain and peripheral tissues. Biochem Biophys Res Commun. 1996; 228:285–292.

4. McDonnell DP, Norris JD. Connections and regulation of the human estrogen receptor. Science. 2002; 296:1642–1644.

5. Heldring N, Pike A, Andersson S, Matthews J, Cheng G, Hartman J, et al. Estrogen receptors: how do they signal and what are their targets. Physiol Rev. 2007; 87:905–931.

6. Filardo EJ, Thomas P. GPR30: a seven-transmembrane-spanning estrogen receptor that triggers EGF release. Trends Endocrinol Metab. 2005; 16:362–367.

7. Prossnitz ER, Arterburn JB, Smith HO, Oprea TI, Sklar LA, Hathaway HJ. Estrogen signaling through the transmembrane G protein-coupled receptor GPR30. Annu Rev Physiol. 2008; 70:165–190.

8. Otto C, Rohde-Schulz B, Schwarz G, Fuchs I, Klewer M, Brittain D, et al. G protein-coupled receptor 30 localizes to the endoplasmic reticulum and is not activated by estradiol. Endocrinology. 2008; 149:4846–4856.

9. Pedram A, Razandi M, Levin ER. Nature of functional estrogen receptors at the plasma membrane. Mol Endocrinol. 2006; 20:1996–2009.

10. Madak-Erdogan Z, Kieser KJ, Kim SH, Komm B, Katzenellenbogen JA, Katzenellenbogen BS. Nuclear and extranuclear pathway inputs in the regulation of global gene expression by estrogen receptors. Mol Endocrinol. 2008; 22:2116–2127.

11. Filardo EJ, Quinn JA, Bland KI, Frackelton AR Jr. Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF. Mol Endocrinol. 2000; 14:1649–1660.

12. Bologa CG, Revankar CM, Young SM, Edwards BS, Arterburn JB, Kiselyov AS, et al. Virtual and biomolecular screening converge on a selective agonist for GPR30. Nat Chem Biol. 2006; 2:207–212.

13. Kanda N, Watanabe S. 17beta-estradiol stimulates the growth of human keratinocytes by inducing cyclin D2 expression. J Invest Dermatol. 2004; 123:319–328.

14. Ylikomi T, Vienonen A, Ahola TM. G protein-coupled receptor 30 down-regulates cofactor expression and interferes with the transcriptional activity of glucocorticoid. Eur J Biochem. 2004; 271:4159–4168.

15. Ji TH, Grossmann M, Ji I. G protein-coupled receptors. I. Diversity of receptor-ligand interactions. J Biol Chem. 1998; 273:17299–17302.