Acute therapy with megestrol acetate decreases nuclear and cytosol androgen receptors in human BPH tissue.

This study measures the effect of megestrol acetate (Megace), a progestational antiandrogen, on nuclear and cytosol receptor concentrations in human BPH prostates. Prostatic tissue was obtained at surgery from both untreated patients with BPH and patients pretreated for three to eleven days with 120 to 160 mg of Megace daily; tissues were homogenized and separated into cytosol and crude nuclear fractions. Cytosol and salt extractable nuclear fractions were subjected to saturation analysis with 3H R1881 over the range of 0.5 to 10 nmoles in exchange reactions for 20 hours at 15 degrees C. Cytosol receptor concentration decreased significantly from 32.7 to 8.7 femtomoles per mg protein (P less than 0.05); nuclear receptor also was significantly reduced from 317 to 43.8 femtomoles (fmole) per mg DNA (P less than .001). Plasma testosterone also decreased significantly from 3.65 to 1.01 ng/ml in Megace-treated patients. These effects of Megace on receptor concentration appear to be qualitatively quite different from those reported following castration in animals or following high-dose estrogen therapy in humans. The mechanism of action of Megace in decreasing both cytosol and nuclear androgen receptor concentrations is unknown. It is possible that decrease in receptor concentration is secondary to either the progestational or antiandrogenic effects of Megace. These possibilities are currently under study.