Differential regulation of Akt phosphorylation in endometriosis.
Protein kinase B (PKB/Akt), a serine/threonine kinase, regulates the function of many cellular proteins involved in apoptosis and proliferation. It was postulated that there is a higher Akt activity in endometriosis compared with normal endometrium, and that oestrogen may be one of the factors responsible for the high Akt activation in endometriotic cells. Phospho-Akt (pAkt) concentrations in normal, eutopic and ectopic endometrial tissues were compared by immunohistochemistry, and a higher pAkt immunoreactivity was revealed in eutopic and ectopic endometrium compared with normal endometrium, in vivo. Higher Akt phosphorylation in stromal cells from eutopic endometrium was observed, when compared with normal, in vitro (P < 0.05). Akt phosphorylation was rapidly (2-10 min) stimulated when endometrial stromal cells from normal and endometriosis patients were treated with 17 beta-oestradiol. In endometrial stromal cells from the endometriosis group, ICI 182,780 (ICI, a specific oestrogen receptor antagonist) failed to antagonize the effect of oestradiol when combined with oestradiol, and revealed a stimulatory effect on Akt phosphorylation when given alone (P < 0.05). In conclusion, since Akt affects cell survival, it is suggested that increased Akt phosphorylation may be related to the altered apoptosis/proliferation harmony in endometriosis, and therefore Akt may play a critical role in the pathogenesis of endometriosis.
Cinar
Ozgur
O
Centre for Assisted Reproductive Medicine and IVF, Etlik Zubeyde Hanim Women's Health Teaching and Research Hospital, Ankara 06010, Turkey.
Seval
Yasemin
Y
Uz
Yesim H
YH
Cakmak
Hakan
H
Ulukus
Murat
M
Kayisli
Umit A
UA
Arici
Aydin
A
D000730:Androstadienes / Q000494:pharmacology; D004715:Endometriosis / Q000378:metabolism*; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D000077191:Wortmannin
D000730:Androstadienes; D000077267:Fulvestrant; D004958:Estradiol; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin