Agonistic activity of ICI 182 780 on activation of GSK 3ß/AKT pathway in the rat uterus during the estrous cycle.
Steroids
; 78(7): 717-25, 2013 Jul.
Article
em En
| MEDLINE
| ID: mdl-23583603
We examined the ability of ICI 182,780 (ICI) to block uterine cell proliferation via protein kinase b/AKT pathway in the uterus of the rat during the estrous cycle. Intact rats, with regular estrous cycles, received a subcutaneous (s.c.) injection of either vehicle or ICI at 08:00 h on the day of proestrus or at 00:00 h on the day of estrus and sacrificed at 13:00 h of metaestrus. Estradiol (E2) and progesterone (P4) plasma levels were measured by radioimmunoassay. Both ICI treatments, induced a significant decrease (p<0.01) in uterine estrogen receptor alpha (ERα) content, had no effect on uterine progesterone receptor (PR) protein expression and caused marked nuclear localization of cyclin D1, in both luminal and glandular uterine epithelium, as compared to vehicle-treated animals. Furthermore, we detected that ICI treatment induced glycogen synthase kinase (Gsk3-ß) Ser 9 phosphorylation, which correlates with cyclin D1 nuclear localization. However, some differences were observed between the two different time schedules of administration. We observed that the administration of ICI at 08:00 h on proestrus day produced a 15% inhibition of luminal epithelial cell proliferation, reduced uterine wet weight by 21% and caused reduction of Akt phosphorylation at Ser 473 as compared to vehicle-treated animals, whereas ICI treatment at 00:00 h on estrus day had no effect on these parameters. The overall results indicate that ICI may exert agonistic and antagonistic effects on uterine cell proliferation through differential activation of the Akt pathway depending on the administration period during the estrous cycle, and indicates that the mechanism of cell proliferation during the physiological conditions of the estrous cycle, is under a different and more complex regulation than in the ovariectomized + E2 animal model.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Útero
/
Ciclo Estral
/
Quinase 3 da Glicogênio Sintase
/
Estradiol
/
Proteínas Proto-Oncogênicas c-akt
Limite:
Animals
Idioma:
En
Revista:
Steroids
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
México
País de publicação:
Estados Unidos