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Endocrinology Vol. 142, No. 6 2458-2467
Copyright © 2001 by The Endocrine Society

ARTICLES

Elevated Androgens and Prolactin in Aromatase-Deficient Mice Cause Enlargement, But Not Malignancy, of the Prostate Gland1

Stephen J. McPherson, Hong Wang, Margaret E. Jones, John Pedersen, Tiina P. Iismaa, Nigel Wreford, Evan R. Simpson and Gail P. Risbridger

Center for Urological Research, Monash Institute of Reproduction and Development (S.J.M., H.W., G.P.R.), and Department of Anatomy (N.W.), Monash University, and Prince Henry’s Institute of Medical Research, Monash Medical Center (M.E.J., E.R.S.), Clayton, Victoria 3168; Melbourne Pathology (J.P.), Collingwood, Victoria 3066; and Garvan Institute of Medical Research (T.P.I.), Sydney, New South Wales 2010, Australia

Address all correspondence and requests for reprints to: Prof. G. P. Risbridger, Monash Institute of Reproduction and Development, 27–31 Wright Street, Clayton, Victoria 3168, Australia. E-mail: gail.risbridger{at}med.monash.edu.au

Although androgens are the main steroids controlling the growth of the mammalian prostate, increasing evidence demonstrates that estrogens also regulate prostate development and growth. This study describes the effects of estrogen deficiency using aromatase knockout mice (ArKO) with targeted disruption of the cyp19 gene. Serum and tissue testosterone and 5{alpha}-dihydrotestosterone as well as serum PRL levels are significantly (P < 0.05) elevated in mature male ArKO mice. Histological, stereological, and immunohistochemical studies demonstrated enlargement of the ventral, anterior, and dorsolateral lobes of the prostate in young and older ArKO mice. Hyperplasia of the epithelial, interstitial, and luminal compartments was identified and associated with up-regulation of androgen receptors. There was no evidence of malignancy as the animals aged (up to 56 weeks). The changes observed in the prostates of ArKO mice were unaffected by maintaining mice on regular or soy-free diets. It is concluded in ArKO mice that, despite the long-term elevation of androgens and PRL, the absence of estrogen in these animals does not result in induction of malignancy in the prostate gland.




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