Immunohistochemical evaluation of uteri from female rhesus monkeys (MACACA MULATTA) after cyclic intramuscular estrogen treatment

Abstract

To evaluate the immunohistochemical parameters of estrogen receptor-α (ERα) and progesterone receptor (PR) in the uteri of perimenopausal female rhesus monkeys that underwent ovariectomies (OVXs) and were then randomized to receive intramuscular 17β-estradiol treatment (E). A prospective, randomized double-blinded study. Monkeys underwent OVXs and were randomly assigned to age-matched OVX plus E or OVX plus placebo vehicle (V) treatment groups. After a post-OVX interval of 30 ± 1.7 weeks (mean ± SEM), 15 monkeys received E (100 μg/ml) and 13 monkeys received V every 3 weeks for 2 to 3 years. Paraffin sections of the uterine corpus and lower uterine segment (LUS) were stained using standard techniques for ERα and PR. Immunohistochemical evaluation of glandular (G), myometrium (M), and stromal (S) compartments were performed separately on uterine corpus and LUS regions. Scoring of immunopositivity for ERα and PR were performed by multiplying the percentage of positive cells (0–25% = 1, 26–50% = 2, 51–75% = 3, and 76–100% = 4) by the intensity of staining (graded 1–4). Repeated measures analysis via SAS's Proc Mixed was used on natural log transformed data. Geometric means and their ratios are reported and were obtained by exponentiating the mixed model estimates. The uterine histology from E and V treated monkeys revealed no evidence of hyperplasia or cancer. The interaction between treatment effect and the repeated measure effect of group and the P-value for interaction was significant: P=0.017. TableGroup EGroup VRatio of GeometricGeometric MeanGeometric MeanMeans (E/V)P-value95% CIERα Corpus S1.00002.33750.42780.00720.2352, 0.7782ERα LUS S1.00002.46550.40560.00350.2277, 0.7224PR Corpus M9.15772.55393.58580.00031.9160, 6.7110PR LUS G13.88058.29521.67330.03831.0304, 2.7174PR LUS M7.38352.18803.37460.00021.8789, 6.0610PR LUS S7.44172.84132.61920.01541.2207, 5.6197 Open table in a new tab E administration in ovariectomized monkeys results in a significant decrease in ERα in the S compartment of both the uterine corpus and LUS, and a significant increase in PR in the LUS in the G, M, and S compartments. These findings demonstrate E administration plays a significant role in uterine physiology and results in the differential expression of ERα and PR in the female rhesus monkey.