Nuclear progestin receptors in normal and malignant human endometrium.

ABSTRACT

PIP The use of medroxyprogesterone acetate (MPA) was incorporated into a nuclear receptor assay for progestin receptor in human endometrium. The assay was developed because MPA is a better ligand than progesterone since it does not bind to corticosteroid-binding globulin and gives greater kinetic stability to the nuclear complex. The MPA nuclear receptor complex for malignant endometrium dissociated at a faster rate than did the complex obtained from normal endometrium, an alteration in binding kinetics which could not be explained by instability of the receptors from malignant endometrium. Factors, including radiation therapy, plasma proteins, endogenous steroids, receptor degradation, tissue heterogeneity, and limited sample size, which influence the interpretation of receptor assay were systematically evaluated. In spite of these controls, it would be premature to conclude that the clinical observations indicate altered receptor from malignant tissue. Further studies are required on endometrial carcinoma which is free of normal tissue fragments. Clinically, nuclear receptor levels were highest in normal endometrium but decreased in samples of malignant endometrium as tumors became more anaplastic. The lowest nuclear binding activity was detected in samples of metastatic endometrial tissue (carcinoma). Hopefully, this nuclear receptor assay (which uses MPA because its dissociation was slower than progesterone) will provide data for correlating clinical response to therapy.^ieng