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This version published online on June 10, 2004
Endocrinology, doi:10.1210/en.2004-0526
A more recent version of this article appeared on September 1, 2004
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Submitted on April 23, 2004
Accepted on June 4, 2004

Differential Effects of TGF{beta}1 on Cellular Proliferation in the Developing Prostate

Darren C. Tomlinson, Sarah H. Freestone, O. Cathal Grace, and Axel A. Thomson*

MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The University of Edinburgh Chancellor's Building, 49 Little France Crescent, Old Dalkeith Road, Edinburgh, EH16 4SB, UK, Tel +44 131 242 6221, Fax +44 131 242 6231

* To whom correspondence should be addressed. E-mail: axel.thomson{at}hrsu.mrc.ac.uk.

Transforming growth factor {beta} 1 (TGF{beta}1) plays an important role in the growth of the prostate, and has been reported to stimulate or inhibit proliferation of prostatic epithelia. We show here that Tgf{beta}1, Tgf{beta}2 and Tgf{beta}3 mRNA expression correlated with developmental growth of the prostate. Recombinant TGF{beta}1 inhibited the growth of the prostate when added to cultures of ventral prostate (VP) organs grown in vitro. Interestingly, TGF{beta}1 had contrasting effects upon cellular proliferation; it stimulated proliferation at the periphery of the organs (distal to urethra) but inhibited proliferation in the center of the organs (proximal to urethra). We speculate that differential effects upon proliferation may be determined by the level of cellular differentiation, since cells at the periphery are undifferentiated while those in the center are more highly differentiated. TGF{beta}1 also stimulated branching morphogenesis at growing ductal tips at the perimeter of the VP. To investigate potential mechanisms of TGF{beta}1 action, we examined the three dimensional distribution of smooth muscle in prostatic organs following treatment with TGF{beta}1. TGF{beta}1 showed a significant effect upon the distribution of smooth muscle within VPs which may mediate part of its' effect upon proliferation. Finally, we addressed how testosterone and TGF{beta}1 might affect gene expression in our developmental system. Testosterone repressed the expression of Tgf{beta}2 mRNA in the prostate, while TGF{beta}1 showed a modest repression of Fgf10 mRNA. It appeared that effects of these factors were more pronounced in a model of prostatic mesenchyme devoid of epithelia compared with prostatic organs (containing epithelia).


Key words: prostate • prostate development • TGF{beta} • smooth muscle • FGF10




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