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This version published online on April 10, 2003
Endocrinology, doi:10.1210/en.2003-0068
A more recent version of this article appeared on July 1, 2003
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*Prostate Cancer

Submitted on January 16, 2003
Accepted on April 1, 2003

Prostate Development and Carcinogenesis in Prolactin Receptor Knockout Mice

Fiona G. Robertson1, Jessica Harris1, Matthew J. Naylor1, Samantha R. Oakes1, Jon Kindblom1, Karin Dillner1, Håkan Wennbo1, Jan Törnell1, Paul A. Kelly1, Jeff Green1, and Christopher J. Ormandy1*

1 Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, 2010, Sydney, AUSTRALIA; Department of Physiology, Research Center for Endocrinology and Metabolism, Göteborg University, SWEDEN, INSERM Unité 344, Faculté de Médecine Necker-Enfants Malades, Paris FRANCE and Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, USA.

* To whom correspondence should be addressed. E-mail: c.ormandy{at}garvan.org.au.

Hyperprolactinemia results in prostatic hypertrophy and hyperplasia, but it is not known whether prolactin plays an essential role in these processes in the prostate. To address this question we have investigated prostate development, gene expression and SV40T-induced prostate carcinogenesisis in prolactin receptor knockout mice. These animals showed a small increase in dorsolateral and ventral prostate weight, but no change in the weight of the anterior prostate. The dorsal, but not ventral or lateral lobes showed a 12% loss of epithelial cells, all other morphological parameters were normal. The area of SV40T-induced prostate intraepithelial neoplasia was reduced by 28% in the ventral lobe but not the dorsal lobe, and no tumors were seen in 20 prolactin receptor knockout animals compared with 1/11 detected in wild-type and 4/21 found in heterozygous animals. Oligonucleotide microarrays were used to identify essential transcriptional roles of prolactin, and revealed a small set of genes with decreased expression involved in sperm/oocyte interaction and copulatory plug formation. Infertility or reduced fertility was apparent in these animals. These findings establish essential though subtle roles for prolactin in the regulation of prostate morphology, gene expression, SV40T-induced neoplasia and reproductive function.


Key words: Prostate prolactin prostate intraepithelial neoplasia SV40T knockout mice




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