Akt/protein B and estradiol receptor alpha expressions in postmenopausal endometrium.

Objective: Estrogen receptor interacts in several types of cells with phosphatidyl-inositol 3-kinase/Akt pathway regulating cell survival and apoptosis. No data are available of the Akt/PKB signaling and its role in the endometrial homeostasis of the postmenopausal uterus. The aim of the present investigation was to study the Akt/protein kinase B signaling in tissue samples retrieved from postmenopausal endometrium of the human uterus with parallel observation of the changes of the expression and phosphorylation of ERalpha.

Study Design: Sixty disease-free postmenopausal women were enrolled in the study. Endometrial tissue samples were obtained from diagnostic curettage or direct from the uterus after hysterectomy done for benign uterine lesions other than endometrial disease. For comparison, the studied parameters were also analyzed in endometrial samples of women with regular menstrual cycles (n=16). In each individual tissue sample the expression and phosphorylation of ERalpha, Akt, and cyclin D1 was analyzed by Western blotting.

Results: The level of Akt protein did not show significant change, however, the activation of Akt proteins and the expression of ERalpha increased parallel with serum estrogen (E2) levels, suggesting the role of E2 in Akt activation and ERalpha expression. The level of pERalpha(Ser167) changed parallel with pAkt(Ser473) levels. Significant correlation was found between the changes of pERalpha and ERalpha (r=0.650399, p<0.005), and in that of pERalpha and pAkt (r=0.639643, p<0.007), respectively. The expression of cyclin D1 was increased in samples with elevated pAkt levels.

Conclusion: The results are indicating that the postmenopausal endometrium responds to E2 by both genomic and nongenomic mechanism. The interaction between ERalpha and Akt plays crucial role in the regulation of proliferative activity in postmenopausal endometrium.