A role for estrogen receptor ss in the regulation of growth of the ventralprostate

Citation
Wh. Zhang et al., A role for estrogen receptor ss in the regulation of growth of the ventralprostate, P NAS US, 98(11), 2001, pp. 6330-6335
Citations number
34
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN journal
0027-8424 → ACNP
Volume
98
Issue
11
Year of publication
2001
Pages
6330 - 6335
Database
ISI
SICI code
0027-8424(20010522)98:11<6330:ARFERS>2.0.ZU;2-G
Abstract
In normal rats and mice, immunostaining with specific antibodies revealed t hat nuclei of most prostatic epithelial cells harbor estrogen receptor beta (ER beta). In rat ventral prostate, 530- and 549-aa isoforms of the recept or were identified. These sediment in the 45 region of low-salt sucrose gra dients, indicating that prostatic ER beta does not contain the same protein chaperones that are associated with ER alpha. Estradiol (E-2) binding and ER beta immunoreactivity coincide on the gradient, with no indication of ER alpha. In prostates from mice in which the ER beta gene has been inactivat ed (BERKO), androgen receptor (AR) levels are elevated, and the tissue cont ains multiple hyperplastic foci, Most epithelial cells express the prolifer ation antigen Ki-67, In contrast, prostatic epithelium from wild-type litte rmates is single layered with no hyperplasia, and very few cells express Ki -67. Rat ventral prostate contains an estrogenic component, which comigrate s on HPLC with the testosterone metabolite 5 alpha -androstane-3 beta ,17 b eta -diol (3 beta Adiol). This compound, which competes with E-2 for bindin g to ER beta and elicits an estrogenic response in the aorta but not in the pituitary, decreases the AR content in prostates of wild-type mice but doe s not affect the elevated levels seen in ER beta knockout (BERKO) mice. Thu s ER beta, probably as a complex with 3 beta Adiol, is involved in regulati ng the AR content of the rodent prostate and in restraining epithelial grow th. These findings suggest that ligands specific for ER beta may be useful in the prevention and/or clinical management of prostatic hyperplasia and n eoplasia.