Failure of down-regulation of estrogen receptors and progesterone receptors after medroxyprogesterone acetate administration for endometrial hyperplasias.

BACKGROUND

To determine the biologic difference between normal endometrium and endometrial hyperplasias, the authors assessed the expression of estrogen receptors (ER) and progesterone receptors (PR) in the subjects before and after oral administration of medroxyprogesterone acetate (MPA) (Hysron-H, Kyowa Hakko Kogyo Co., Ltd., Tokyo, Japan).

METHODS

The authors studied the expression of ER and PR in pathologic conditions of the endometrium such as cystic, adenomatous, and atypical hyperplasias before and after MPA treatment, 600 mg daily, for 8-14 weeks, and compared this expression with that of normal endometrium.

RESULTS

Stromal and epithelial components of the normal endometrium in the proliferative phase were positive for ER and PR. In the secretory phase and after MPA treatment, the epithelial component showed either negative or faint staining for ER and PR, but the stromal component showed positive staining for PR and negative or faint staining for ER. All hyperplasias exhibited ER and PR in the stromal and epithelial components, although the intensity of the staining was variable in atypical hyperplasias. After MPA treatment, in the epithelial component of cystic and adenomatous hyperplasias, down-regulation of PR was prominent, but many cells continued to express ER. The epithelial component usually was surrounded by PR-positive decidual cells. In atypical hyperplasia, many cells continued to express ER and PR in the epithelial component surrounded by both ER and PR positive stromal cells after MPA treatment.

CONCLUSIONS

Among the pathologic conditions of the endometrium, cystic and adenomatous hyperplasias have mechanisms of down-regulation of PR but not ER in the glandular component after MPA treatment, whereas in atypical hyperplasia, down-regulation of ER and PR does not occur in the epithelial component. Compared with normal endometrium, the majority of endometrial hyperplasias have an impairment of down-regulation of ER in the epithelial component by MPA treatment, and atypical hyperplasia has an impairment of down-regulation of ER and PR. Endometrial hyperplasias seem to have an abnormality of down-regulatory mechanisms of sex steroid receptors in the epithelial component when treated with exogenous progesterone.