An endocrine pathway in the prostate, ERβ, AR, 5α-androstane-3β,17β-diol, and CYP7B1, regulates prostate growth

Abstract

Epithelial proliferation of the ventral prostate in rodents peaks between 2 and 4 weeks of age, and by week 8, proliferating cells are rare. We have used ERβ^−/− and CYP7B1^−/− mice to investigate the role of ERβ and one of its ligands, 5α-androstane-3β,17β-diol (3βAdiol), in growth of the ventral prostate. Before puberty, ERβ was found in quiescent but not in proliferating cells, and proliferating cells occurred more frequently in ventral prostates of ERβ^−/− mice than in wild-type littermates. Treatment with 3βAdiol decreased proliferation in wild-type but not in ERβ^−/− mice. In rats, treatment with 3βAdiol from postnatal day 2 to 28 resulted in reduction in growth of ventral prostates. The prostates of CYP7B1^−/− mice were hypoproliferative before puberty and smaller than those of their wild-type littermates after puberty. Because CYP7B1 represents the major pathway for inactivating 3βAdiol in the prostate, we suggest that ERβ, 3βAdiol, and CYP7B1 are the components of a pathway that regulates growth of the rodent ventral prostate. In this pathway, ERβ is an antiproliferative receptor, 3βAdiol is an ERβ ligand, and CYP7B1 is the enzyme that regulates ERβ function by regulating the level of 3βAdiol.