Effect of estrogen and progesterone on the development of endometrial hyperplasia in the Fischer rat

The effect of changing endocrine status on the uterine endometrium of the female Fischer rat was observed in vivo after neonatal androgenization, after aging, after estrogen (E) implant in ovariectomized (OVX) rats, and in vitro after progesterone (P) addition to monolayer cultures of uterine tumor cells. Neonatal androgenization produced cystic ovarian follicles and persistent vaginal cornification for 10-14 mo, indicative of an anovulatory, persistent E status. The constant estrous (CE) state, induced by androgenization, uniformly produced focal glandular hyperplasia of the endometrium at 9 mo of age. Focal glandular hyperplasia, which was absent in the cycling 6-mo-old estrous endometrium, was also apparent in the 12-mo-old rats which had ceased cycling and entered natural CE. Subcutaneous estradiol-17 beta (E2) implants in 12-mo-old OVX rats induced early cystic and adenomatous changes in the foci of hyperplasia. Acyclic control rats, 21 mo old, in persistent diestrus (PD) exhibited a 3-fold elevation of serum P associated with glandular atrophy of the endometrium. Ten nM P also inhibited proliferation of endometrial cells in cultures prepared from tumors of 21-mo-old rats. On the other hand, adenomatous hyperplasia was observed in 29-mo-old PD rats, despite the presence of low serum E and elevated serum P. These results indicate that either induced or natural constant E status leads to focal glandular hyperplasia in the Fischer rat. E2 implants in the 12-mo-old OVX Fischer rat induced early cystic and adenomatous changes in the focal hyperplasia. Inhibition of these focal hyperplasias was associated with elevated serum P at 21 mo. The development of adenomatous hyperplasia in the aged endometrium, on the other hand, occurred despite elevated serum P at 29 mo.