Estradiol increases the Bax/Bcl-2 ratio and induces apoptosis in the anterior pituitary gland.
BACKGROUND
Estrogens are recognized as acting as modulators of pituitary cell renewal, sensitizing cells to mitogenic and apoptotic signals, thus participating in anterior pituitary homeostasis during the estrous cycle. The balance of pro- and antiapoptotic proteins of the Bcl-2 family is known to regulate cell survival and apoptosis.


OBJECTIVE
In order to understand the mechanisms underlying apoptosis during the estrous cycle, we evaluated the expression of the proapoptotic protein Bax and the antiapoptotic proteins Bcl-2 and Bcl-xL in the anterior pituitary gland in cycling female rats as well as the influence of estradiol on the expression of these proteins in anterior pituitary cells of ovariectomized rats.


RESULTS
As determined by Western blot, the expression of Bax was higher in anterior pituitary glands from rats at proestrus than at diestrus I, Bcl-2 protein levels showed no difference and Bcl-xL expression was lower, thus increasing the Bax/Bcl-2 ratio at proestrus. Assessed by annexin V binding and flow cytometry, the percentage of apoptotic anterior pituitary cells was higher in rats at proestrus than at diestrus I. Chronic estrogen treatment in ovariectomized rats enhanced the Bax/Bcl-2 ratio and induced apoptosis. Moreover, incubation of cultured anterior pituitary cells from ovariectomized rats with 17beta-estradiol for 24 h increased the Bax/Bcl-2 ratio, decreased Bcl-xL expression and induced apoptosis.


CONCLUSIONS
Our results demonstrate that estradiol increases the ratio between proapoptotic and antiapoptotic proteins of the Bcl-2 family. This effect could participate in the sensitizing action of estrogens to proapoptotic stimuli and therefore be involved in the high apoptotic rate observed at proestrus in the anterior pituitary gland.
Zaldivar
Verónica
V
Instituto de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Magri
María Laura
ML
Zárate
Sandra
S
Jaita
Gabriela
G
Eijo
Guadalupe
G
Radl
Daniela
D
Ferraris
Jimena
J
Pisera
Daniel
D
Seilicovich
Adriana
A
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002452:Cell Count; D004031:Diestrus / Q000502:physiology; D004958:Estradiol / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D030762:Estrous Cycle / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D010052:Ovariectomy; D010903:Pituitary Gland, Anterior / Q000502:physiology*; D011359:Proestrus / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D017304:Annexin A5; C494828:Bax protein, rat; D004967:Estrogens; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D004958:Estradiol