Effects of 17beta-estradiol replacement on the apoptotic effects caused by ovariectomy in the rat hippocampus.
OBJECTIVE
The aim of the present study was to investigate the effects of different periods of ovariectomy and 17beta-estradiol replacement on apoptotic cell death and expression of members of the Bcl-2 family in the rat hippocampus.


METHODS
Hippocampi were obtained from rats in proestrus, ovariectomized (15 days, 21 days and 36 days), ovariectomized for 15 days and then treated with 17beta-estradiol for 7 or 21 days, and rats ovariectomized and immediately treated with 17beta-estradiol for 21 days. The expression of Bcl-2 and Bax and the number of apoptotic cells were determined.


RESULTS
Ovariectomy decreased Bcl-2 expression and increased Bax expression and the number of apoptotic cells. Replacement with 17beta-estradiol (21 days) throughout the post-ovariectomy period reduced the number of apoptotic cells to the control levels, and prevented the effects of ovariectomy on Bax expression, but only partially restored the Bcl-2 expression. After 15 days of ovariectomy, the replacement with 17beta-estradiol for 21 days, but not for 7 days, restored the Bcl-2 and Bax expression and the percentage of apoptotic cells to the levels found in the proestrus control.


CONCLUSIONS
The present results show that a physiological concentration of 17beta-estradiol may help maintain long-term neuronal viability by regulating the expression of members of the Bcl-2 family. Even after a period of hormonal deprivation, treatment with 17beta-estradiol is able to restore the expression of Bax and Bcl-2 to control levels, but the duration of the treatment is a key factor to obtain the desired effect. These data provide new understanding into the mechanisms contributing to the neuroprotective action of estrogen.
Sales
Sayuri
S
Laboratory of Pharmacology, Instituto Butantan, Brazil.
Ureshino
Rodrigo Portes
RP
Pereira
Renato Tavares dos Santos
RT
Luna
Milene Schmidt Amaral
MS
Pires de Oliveira
Marcelo
M
Yamanouye
Norma
N
Godinho
Rosely Oliveira
RO
Smaili
Soraya Soubhi
SS
Porto
Catarina Segreti
CS
Abdalla
Fernando Maurício Francis
FM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects* / Q000503:physiopathology; D010052:Ovariectomy / Q000009:adverse effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D051028:bcl-2-Associated X Protein / Q000032:analysis
D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D004958:Estradiol