An endocrine pathway in the prostate, ERbeta, AR, 5alpha-androstane-3beta,17beta-diol, and CYP7B1, regulates prostate growth.
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.
Weihua
Zhang
Z
Department of Medical Nutrition, Karolinska Institute, Novum, S-141 86 Huddinge, Sweden.
Lathe
Richard
R
Warner
Margaret
M
Gustafsson
Jan-Ake
JA
D015113:Androstane-3,17-diol / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002455:Cell Division; D003577:Cytochrome P-450 Enzyme System / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D047629:Estrogen Receptor beta; D008024:Ligands; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011467:Prostate / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D047629:Estrogen Receptor beta; D008024:Ligands; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D015113:Androstane-3,17-diol; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; C115867:oxysterol 7-alpha-hydroxylase