Evidence for an Androgen-independent Mechanism Regulating the Levels of Receptor in Target Tissue

Abstract

Abstract The amount of radioactive dihydrotestosterone (17β-hydroxy-5α-[1,2-3H]androstan-3-one) bound to high molecular weight molecules in the 8 to 10 S fraction of the 100,000 x g supernatant was measured at intervals following castration. As expected, the receptor concentration (and activity per mg of cytosol protein or per µg of DNA) declined steadily to immeasurable levels by the 4th day following castration. However, whereas the size of the prostate and the DNA content per prostate and per mg of tissue continued to fall, the receptor concentration per mg of tissue and per µg of DNA increased to levels similar to those found 1 day following castration. The maximum was reached by the 8th day after castration and was maintained for at least 6 weeks. The results of the sucrose gradient analysis were confirmed by DEAE-cellulose chromatography. The same phenomenon was observed in animals which were either hypophysectomized or adrenalectomized at the time of castration. This finding indicates that restoration of receptor is not mediated by adrenal androgens or pituitary hormones. These observations suggest that there is an androgen-independent mechanism for providing receptor to receive the androgenic stimulus for growth and development as well as for maintenance of the mature prostate.