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PMID:20445128

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Citation

Lucas, TF, Royer, C, Siu, ER, Lazari, MF and Porto, CS (2010) Expression and signaling of G protein-coupled estrogen receptor 1 (GPER) in rat sertoli cells. Biol. Reprod. 83:307-17

Abstract

The aim of the present study was to investigate the expression and signaling of the G protein-coupled estrogen receptor 1 (GPER) in cultured immature rat Sertoli cells--in which we have previously described the classical estrogen receptors (ESR1 and ESR2). Expression of GPER in cultured Sertoli cells from 15-day-old rats was detected by RT-PCR and immunoassays. Gper transcripts also were present in testes from 5-, 15-, and 120-day-old rats. Short-term treatment of Sertoli cells with 17beta-estradiol (E2), the GPER agonist G-1, or the ESR antagonist ICI 182,780 (ICI) rapidly activated MAPK3/1 (ERK1/2), even after down-regulation of ESR1 and ESR2, suggesting a role for GPER in the rapid E2 action in these cells. MAPK3/1 phosphorylation induced by ICI or G-1 was blocked by pertussis toxin, selective inhibitor of the SRC family of protein tyrosine kinases, metalloprotease inhibitor, MAP2K1/2 inhibitor, and epidermal growth factor receptor (EGFR) kinase inhibitor. Furthermore, E2, but not G-1, induced up-regulation of cyclin D1 in the Sertoli cells. This effect was blocked by ICI. E2 and G-1 decreased BAX and increased BCL2 expression and these effects were blocked by MAP2K1/2 inhibitor and EGFR kinase inhibitor. The pretreatment with ICI did not block the effect of E2. Taken together, these results indicate that in Sertoli cells 1) GPER-mediated MAPK3/1 activation occurs via EGFR transactivation through G protein beta gamma subunits that promote SRC-mediated metalloprotease-dependent release of EGFR ligands, which bind to EGFR and lead to MAPK3/1 phosphorylation; 2) E2-ESRs play a role in Sertoli cell proliferation; and 3) E2-GPER may regulate gene expression involved with apoptosis. ESR and GPER may mediate actions important for Sertoli cell function and maintenance of normal testis development and homeostasis.

Links

PubMed Online version:10.1095/biolreprod.110.084160

Keywords

Animals; Apoptosis/genetics; Cells, Cultured; Cyclopentanes; Enzyme Activation/drug effects; Estradiol/analogs & derivatives; Estradiol/pharmacology; Estrogen Receptor alpha/antagonists & inhibitors; Estrogen Receptor alpha/genetics; Estrogen Receptor alpha/physiology; Gene Expression Regulation/physiology; Male; Mitogen-Activated Protein Kinase 1/metabolism; Mitogen-Activated Protein Kinase 3/metabolism; Phosphorylation/drug effects; Quinolines; RNA, Messenger/analysis; Rats; Rats, Wistar; Receptor, Epidermal Growth Factor/physiology; Receptors, G-Protein-Coupled/agonists; Receptors, G-Protein-Coupled/genetics; Receptors, G-Protein-Coupled/physiology; Reverse Transcriptase Polymerase Chain Reaction; Sertoli Cells/chemistry; Sertoli Cells/physiology; Signal Transduction; Testis/chemistry; Testis/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:GPER1

involved_in

GO:0030520: intracellular estrogen receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:GPER1

involved_in

GO:0030518: intracellular steroid hormone receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:GPER1

involved_in

GO:0001934: positive regulation of protein phosphorylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:GPER1

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:GPER1

involved_in

GO:0045742: positive regulation of epidermal growth factor receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:GPER1

involved_in

GO:0070374: positive regulation of ERK1 and ERK2 cascade

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:GPER

enables

GO:0003707: steroid hormone receptor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:GPER

enables

GO:0005496: steroid binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:GPER

involved_in

GO:0030518: intracellular steroid hormone receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:GPER

enables

GO:0042562: hormone binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:GPER

GO:0007165: signal transduction

ECO:0000316:

UniProtKB:O08878


P

FIG. 5. Signaling pathways involved in MAPK3/1 phosphorylation induced by G-1 in the Sertoli cells.


complete
CACAO 10522

RAT:GPER

involved_in

GO:0045742: positive regulation of epidermal growth factor receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:GPER

involved_in

GO:0070374: positive regulation of ERK1 and ERK2 cascade

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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