EFFECT OF MEDROXYPROGESTERONE ACETATE ON SEX HORMONE-BINDING GLOBULINMESSENGER-RNA EXPRESSION IN THE HUMAN ENDOMETRIAL CANCER CELL-LINE ISHIKAWA

To understand the rationale of high-dose medroxyprogesterone acetate ( MPA) in the treatment of well-differentiated uterine endometrial cance rs, the effect of MPA on intracellular sex hormone-binding globulin (S HBG) mRNA expression in well-differentiated uterine endometrial cancer cell line Ishikawa was determined by competitive reverse transcriptio n-polymerase chain reaction-Southern blot analysis. Estradiol-17 beta (E2, 10(-8)mol/l) did not alter SHBG mRNA expression, but the addition of 10(-10) mol/l MPA increased it, while a high concentration of MPA (10(-6) to 10(-5) mol/l) with or E2 suppressed it. Furthermore, a high dose (10(-6) mol/l) of chlormadinone acetate or danazol with or witho ut E2 significantly suppressed its expression, while MPA was the most effective among the hormones tested. The effect of MPA and the other s teroid hormone analogs on SHBG expression was not mediated via the pro gesterone receptor. These findings suggest that intracellular SHBG sup pression might partly contribute to the abolition of the intracellular estrogen-dominant milieu, and may be involved as one of the mechanism s of the antitumoral effects of high-dose MPA on the development and g rowth of some well-differentiated endometrial cancer cells.