Ovariectomy and 17β-estradiol replacement play a role on the expression of Endonuclease-G and phosphorylated cyclic AMP response element-binding (CREB) protein in hippocampus

Mol Cell Endocrinol. 2014 Jan 25;382(1):227-233. doi: 10.1016/j.mce.2013.09.037. Epub 2013 Oct 9.


The aim of the present study was to investigate the effects of different periods of ovariectomy and 17β-estradiol (E2) replacement on the expression of Cytochrome C, apoptosis inducing factor (AIF) and Endonuclease-G (Endo-G) in mitochondrial and cytosolic fractions obtained from hippocampus of the adult female rats. In addition, the expression of phosphorylated CREB (phospho-CREB) was also analyzed in hippocampus. Ovariectomy or E2 treatment did not change the expression of Cytochrome C and AIF. Ovariectomy (15, 21 and 36 days) decreased the expression of Endo-G in the mitochondrial fractions and increased it in the cytosolic fractions obtained from hippocampus. The treatment with E2 after 15 days of ovariectomy for 7 days or 21 days, and throughout the post-ovariectomy period prevented the effects of ovariectomy on Endo-G expression. Our results suggest that ovariectomy-induced apoptotic cell death in hippocampal tissue could be mediated by Endo-G, but not by AIF, via a caspase-independent apoptotic pathway. Furthermore, ovariectomy decreased the expression of phospho-CREB and the treatment with E2 prevented these effects. In conclusion, E2 may help maintain long-term neuronal viability by regulating the expression of members of the Bcl-2 family. Regulation of Endo-G released from mitochondria, but not of Cytochrome C and AIF, is also involved in the neuroprotective actions of E2. Furthermore, CREB may be involved in the expression of Bcl-2. These data provide new understanding into the mechanisms involved in the neuroprotective role of estrogen.

Keywords: 17β-Estradiol; AIF; CREB; Cytochrome C; Endonuclease-G; Hippocampus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Inducing Factor / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Cytochromes c / metabolism
  • Endodeoxyribonucleases / metabolism*
  • Estradiol / pharmacology*
  • Estrogen Replacement Therapy*
  • Female
  • Hippocampus / drug effects
  • Hippocampus / enzymology
  • Hippocampus / metabolism*
  • Ovariectomy*
  • Phosphorylation / drug effects
  • Rats
  • Rats, Wistar


  • Apoptosis Inducing Factor
  • Cyclic AMP Response Element-Binding Protein
  • Estradiol
  • Cytochromes c
  • Endodeoxyribonucleases
  • endonuclease G