17β-Estradiol activates GPER- and ESR1-dependent pathways inducing apoptosis in GC-2 cells, a mouse spermatocyte-derived cell line

Adele Chimento, Rosa Sirianni, Ivan Casaburi, Carmen Ruggiero, Marcello Maggiolini, Sebastiano Andò, Vincenzo Pezzi

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

In mammals, spontaneous apoptosis is observed particularly in differentiating spermatogonia and in spermatocytes. 17β-Estradiol (E2) in primary rat pachytene spermatocytes (PS) binds estrogen receptor α (ESR1) and GPER to activate EGFR/ERK/c-Jun pathway leading to up regulation of proapoptotic factor bax. Aim of this study was to clarify the effector pathway(s) controlling spermatocytes apoptosis using as model GC-2 cells, an immortalized mouse pachytene spermatocyte-derived cell line, which reproduces primary cells responses to E2. In fact, in GC-2 cells we observed that ESR1 and GPER activation caused rapid ERK and c-Jun phosphorylation, bax up-regulation, events associated with apoptosis. We further investigated the apoptotic mechanism demonstrating that E2, as well as ESR1 and GPER specific agonists, induced sustained ERK, c-Jun and p38 phosphorylation, Cytochrome c release, caspase 3 and endogenous substrate Poly (ADP-ribose) polymerase (PARP) activation and increased expression of cell cycle inhibitor p21. When ESR1 or GPER expression was silenced, E2 was still able to decrease cell proliferation, only the concomitant silencing abolished E2 effect. These results indicate that GC-2 cells are a valid cell model to study E2-dependent apoptosis in spermatocytes and show that E2, activating both ESR1 and GPER, is able to induce an ERK1/2, c-Jun and p38-dependent mitochondrion apoptotic pathway in this cell type.

Original languageEnglish (US)
Pages (from-to)49-59
Number of pages11
JournalMolecular and Cellular Endocrinology
Volume355
Issue number1
DOIs
StatePublished - May 15 2012

Fingerprint

Spermatocytes
Estradiol
Cells
Apoptosis
Cell Line
Phosphorylation
Chemical activation
Mitochondria
Mammals
Poly(ADP-ribose) Polymerases
Cell proliferation
Up-Regulation
Cytochromes c
Caspase 3
Estrogen Receptors
Rats
Spermatogonia
Cell Cycle
Substrates
Cell Proliferation

Keywords

  • Apoptosis
  • ESR1
  • Estrogen
  • GPER
  • Spermatocytes

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Biochemistry

Cite this

17β-Estradiol activates GPER- and ESR1-dependent pathways inducing apoptosis in GC-2 cells, a mouse spermatocyte-derived cell line. / Chimento, Adele; Sirianni, Rosa; Casaburi, Ivan; Ruggiero, Carmen; Maggiolini, Marcello; Andò, Sebastiano; Pezzi, Vincenzo.

In: Molecular and Cellular Endocrinology, Vol. 355, No. 1, 15.05.2012, p. 49-59.

Research output: Contribution to journalArticle

Chimento, Adele ; Sirianni, Rosa ; Casaburi, Ivan ; Ruggiero, Carmen ; Maggiolini, Marcello ; Andò, Sebastiano ; Pezzi, Vincenzo. / 17β-Estradiol activates GPER- and ESR1-dependent pathways inducing apoptosis in GC-2 cells, a mouse spermatocyte-derived cell line. In: Molecular and Cellular Endocrinology. 2012 ; Vol. 355, No. 1. pp. 49-59.
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