A role for estrogen receptor β in the regulation of growth of the ventral prostate
Open accessAbstract
In normal rats and mice, immunostaining with specific antibodies revealed that nuclei of most prostatic epithelial cells harbor estrogen receptor β (ERβ). In rat ventral prostate, 530- and 549-aa isoforms of the receptor were identified. These sediment in the 4S region of low-salt sucrose gradients, indicating that prostatic ERβ does not contain the same protein chaperones that are associated with ERα. Estradiol (E 2 ) binding and ERβ immunoreactivity coincide on the gradient, with no indication of ERα. In prostates from mice in which the ERβ gene has been inactivated (BERKO), androgen receptor (AR) levels are elevated, and the tissue contains multiple hyperplastic foci. Most epithelial cells express the proliferation antigen Ki-67 . In contrast, prostatic epithelium from wild-type littermates is single layered with no hyperplasia, and very few cells express Ki-67 . Rat ventral prostate contains an estrogenic component, which comigrates on HPLC with the testosterone metabolite 5α-androstane-3β,17β-diol (3βAdiol). This compound, which competes with E 2 for binding to ERβ and elicits an estrogenic response in the aorta but not in the pituitary, decreases the AR content in prostates of wild-type mice but does not affect the elevated levels seen in ERβ knockout (BERKO) mice. Thus ERβ, probably as a complex with 3βAdiol, is involved in regulating the AR content of the rodent prostate and in restraining epithelial growth. These findings suggest that ligands specific for ERβ may be useful in the prevention and/or clinical management of prostatic hyperplasia and neoplasia.
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3β-Diol acts by binding and activating ERβ rather than the androgen receptor.
“3β-diol acts by binding and activating estrogen receptor β, rather than an androgen receptor (Weihua et al., 2001).”
From Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017) · cites this paper as Weihua et al., 2001
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Self-citation
- Authors
- Weihua, Z., Mäkelä, S., Andersson, L. C., Salmi, S., Saji, S., Webster, J. I., Jensen, E. V., Nilsson, S., Warner, M., & Gustafsson, J.-Å.
- Affiliations
- University of Helsinki (FI)
- Houston Methodist (US)
- Departments of Medical Nutrition and Biosciences, Karolinska Institute, Novum, Huddinge, S-141 86 Sweden; Institute of Biomedicine, Department of Anatomy, University of Turku, Turku FIN-20520, Finland; Department of Pathology, Haartman Institute, University of Helsinki, Helsinki FIN-00014, Finland; Department of Oncology and Pathology, Karolinska Institute, Huddinge, S-171 76 Sweden; and KaroBio AB, Novum, Huddinge S-141 86, Sweden
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2001-05-22
- Volume
- 98
- Issue
- 11
- Pages
- 6330-6335
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC33468
- OpenAlex
- W2058177423
- Cited by
- 440
- References
- 1
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 3 · 2023: 7 · 2022: 5 · 2021: 7 · 2020: 3 · 2019: 6 · 2018: 11 · 2017: 6 · 2016: 14 · 2015: 20 · 2014: 8 · 2013: 18 · 2012: 21
- FWCI
- 19.53
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Johns Hopkins University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Health Sciences › Medicine › Urology › Urinary Bladder and Prostate Research
- Keywords
- estrogen receptor beta, ventral prostate, prostatic hyperplasia, androgen receptor, estrogenic activity, Ki-67, ERβ knockout mice, prostatic neoplasia, ERβ isoforms, molecular chaperones
- MeSH terms
- Animals, Centrifugation, Density Gradient, Estrogens, Male, Prostate, Receptors, Estrogen, Sucrose, Androstane-3,17-diol, Rats, Sprague-Dawley, Mice, Knockout, Ki-67 Antigen, Protein Isoforms, Estrogen Receptor beta, Mice, Rats
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