Estrogen replacement therapy induces telomerase RNA expression in the macaque endometrium

Abstract

Objective: To evaluate the effects of hormonal therapies on the expression of telomerase RNA (TRNA) in the endometrium of ovariectomized female cynomolgus macaques ( Macaca fascicularis). Design: Randomized long-term experimental trial. Setting: Animal study at an academic research institution. Patient(s): Surgically postmenopausal cynomolgus macaques. Intervention(s): Treatments were given in the diet for three years and included conjugated equine estrogens (CEE), CEE + medroxyprogesterone acetate (MPA), and tamoxifen, at clinically relevant doses. Main Outcome Measure(s): Expression of TRNA within the basal glands, basal stroma, superficial glands, and superficial stroma of the endometrium by radiolabeled in situ hybridization. Result(s): Conjugated equine estrogens increased glandular TRNA expression, and the addition of MPA decreased this effect. Tamoxifen induced glandular TRNA expression to a lesser degree. Both CEE + MPA and tamoxifen increased stromal TRNA expression. The expression of TRNA in the endometrial glands was always greater than TRNA expression in the stroma. Treatment groups with greater proliferation and progesterone receptor expression also had elevated TRNA; within-group correlations were not significant. No statistically significant difference occurred between the basal and superficial endometrial layers. Conclusion(s): These results show for the first time a cell-specific hormonal regulation of TRNA in the primate endometrium, with up-regulation of TRNA by treatments associated with increased risk of endometrial cancer in women.