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Nuclear Progestin Receptors in Normal and Malignant Human Endometrium^*

PETER D FEIL, WILLIAM J MANN, JR., RODRIGUE MORTEL and C.WAYNE BARDIN

Departments of Medicine, Biochemistry, and Obstetrics and Gynecology, The Milton S. Hershey Medical Center, The Pennsylvania State University Hershey, Pennsylvania 17033

Address requests for reprints to: Dr. Peter D. Feil, Division of Endocrinology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, Pennsylvania 17033.

A nuclear progestin receptor assay was developed for human endometrium using [³H]medroxyprogesterone acetate (MPA). MPA is a better ligand than progesterone since it does not bind to corticosteroid-binding globulin (CBG) and imparts greater kinetic stability to the nuclear complex. Thus, the rate of dissociation of the MPA nuclear receptor complex was slower than that with progesterone. The MPA nuclear receptor complex for malignant endometrium, however, dissociated at a faster rate than did the complex obtained from normal endometrium. This unexpected alteration in binding kinetics could not be explained by instability of the receptors from malignant endometrium. Factors which could influence the interpretation of the receptor assay were systematically evaluated. They included radiation therapy, plasma proteins, endogenous steroids, receptor degradation, tissue heterogeneity, and limited sample size.

This assay was employed to measure receptor concentrations in samples from women with normal and malignant endometria. 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 carcinoma. The nuclear receptor assay should provide a data base which can be correlated with clinical response to therapy. (J Clin Endocrinol Metab 48: 327, 1979)

^* This work was supported by Contract 1-1-2228 from the NIH and in part by Grant 1P30-CA-18450-01 awarded by the National Cancer Institute, DHEW and PHS Grant 5-R10-CA-16386-02.

Recipient of an ACOG-Ortho fellowship.

Recipient of a Josiah Macy foundation scholarship award.

Received April 3, 1978.