Estrogen replacement therapy induces telomerase RNA expression in the macaque endometrium.
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).


METHODS
Randomized long-term experimental trial.


METHODS
Animal study at an academic research institution.


METHODS
Surgically postmenopausal cynomolgus macaques.


METHODS
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.


METHODS
Expression of TRNA within the basal glands, basal stroma, superficial glands, and superficial stroma of the endometrium by radiolabeled in situ hybridization.


RESULTS
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.


CONCLUSIONS
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.
Vidal
Justin D
JD
Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg, Virginia, USA.
Register
Thomas C
TC
Gupta
Madhu
M
Cline
J Mark
JM
D000818:Animals; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D015914:Estrogen Replacement Therapy / Q000662:veterinary*; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D019394:Ki-67 Antigen / Q000032:analysis; D008252:Macaca fascicularis / Q000378:metabolism*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis* / Q000235:genetics; D011897:Random Allocation; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics
D004966:Estrogens, Conjugated (USP); D019394:Ki-67 Antigen; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D012313:RNA; D017258:Medroxyprogesterone Acetate; D019098:Telomerase