Endocrinology, Vol 123, 2124-2131, Copyright © 1988 by Endocrine Society

ARTICLES

Identification of a cellular receptor for transforming growth factor- beta in rat ventral prostate and its negative regulation by androgens

N Kyprianou and JT Isaacs
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.

Scatchard analyses of the binding of transforming growth factor-beta (TGF beta) to membranes from rat ventral prostate revealed the presence of high affinity (Kd = 140 pM) saturable binding sites for [125I]TGF beta. The binding of [125I]TGF beta to prostatic membranes, while displaced in the presence of excess unlabeled TGF beta, is unaffected by epidermal growth factor, nerve growth factor, fibroblast growth factor, or insulin, indicating the specificity of binding. Affinity labeling of these membrane receptors by covalent attachment to [125I]TGF beta with bis-(sulfosuccinimidyl)suberate and subsequent electrophoretic analysis of the labeled complexes revealed the specific binding of [125I]TGF beta to a macromolecule that predominantly migrates as a 260,000 mol wt band in 7.5% acrylamide gels. Castration- induced androgen deprivation produced a significant increase in [125I]TGF beta binding to prostatic membranes with no apparent change in the affinity of membrane receptors for TGF beta. TGF beta receptor levels per total gland increased approximately 2-fold by 3 days after castration, reached a peak value by day 4, and then declined during the subsequent 10 days. Androgen administration to 4-day castrated animals decreased the number of TGF beta receptors to a value similar to that in the intact controls. These results demonstrate the presence of specific binding sites for TGF beta in the rat ventral prostate. Furthermore, the TGF beta receptor levels seem to be under negative androgenic regulation, indicating a potential role for this growth factor in the mechanism of activation of castration-induced death of androgen-dependent epithelial cells in the ventral prostate.

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