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Updated: Aug 6, 2026

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
An endocrine pathway in the prostate, ERbeta, AR, 5alpha-androstane-3beta,17beta-diol, and CYP7B1, regulates prostate
Zhang Weihua1, Richard Lathe, Margaret Warner
1Department of Medical Nutrition, Karolinska Institute, Novum, S-141 86 Huddinge, Sweden.
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 ERbeta(-/-) and CYP7B1(-/-) mice to investigate the role of ERbeta and one of its ligands, 5alpha-androstane-3beta,17beta-diol (3betaAdiol), in growth of the ventral prostate. Before puberty, ERbeta was found in quiescent but not in proliferating cells, and proliferating cells occurred more frequently in ventral prostates of ERbeta(-/-) mice than in wild-type littermates. Treatment with 3betaAdiol decreased proliferation in wild-type but not in ERbeta(-/-) mice. In rats, treatment with 3betaAdiol 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 3betaAdiol in the prostate, we suggest that ERbeta, 3betaAdiol, and CYP7B1 are the components of a pathway that regulates growth of the rodent ventral prostate. In this pathway, ERbeta is an antiproliferative receptor, 3betaAdiol is an ERbeta ligand, and CYP7B1 is the enzyme that regulates ERbeta function by regulating the level of 3betaAdiol.
Insights
Estrogen receptor beta (ERbeta) acts as an antiproliferative receptor in the rodent ventral prostate. Its ligand, 3beta-diol, and the enzyme CYP7B1 are key components regulating prostate growth.
Area of Science:
- Endocrinology
- Molecular Biology
- Urology
Background:
- Ventral prostate epithelial proliferation in rodents is age-dependent, peaking early and declining by 8 weeks.
- Estrogen receptor beta (ERbeta) and its ligand 5alpha-androstane-3beta,17beta-diol (3betaAdiol) are implicated in prostate growth regulation.
Purpose of the Study:
- To investigate the roles of ERbeta and 3betaAdiol in rodent ventral prostate growth.
- To elucidate the function of CYP7B1 in the ERbeta-mediated prostate growth pathway.
Main Methods:
- Utilized ERbeta(-/-) and CYP7B1(-/-) knockout mice models.
- Administered 3betaAdiol to wild-type and knockout mice.
- Analyzed ventral prostate proliferation and size in rodents at different ages and treatments.
Main Results:
- ERbeta was present in quiescent, not proliferating, prostate cells before puberty.
- ERbeta(-/-) mice exhibited increased ventral prostate proliferation compared to wild-type.
- 3betaAdiol treatment reduced proliferation in wild-type but not ERbeta(-/-) mice, and decreased ventral prostate growth in rats.
- CYP7B1(-/-) mice showed hypoproliferative and smaller ventral prostates.
Conclusions:
- ERbeta functions as an antiproliferative receptor in the ventral prostate.
- 3betaAdiol acts as an ERbeta ligand, and CYP7B1 regulates its levels, controlling ERbeta-mediated prostate growth.
- ERbeta, 3betaAdiol, and CYP7B1 form a critical pathway for rodent ventral prostate growth regulation.
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