This Article Full Text Full Text (PDF) All Versions of this Article: 144/7/3196    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Robertson, F. G. Articles by Ormandy, C. J. Search for Related Content PubMed PubMed Citation Articles by Robertson, F. G. Articles by Ormandy, C. J.

Prostate Development and Carcinogenesis in Prolactin Receptor Knockout Mice

Cancer Research Program (F.G.R., J.H., M.J.N., S.R.O., C.J.O.), Garvan Institute of Medical Research, St. Vincent’s Hospital, Darlinghurst, 2010 Sydney, Australia; Department of Physiology (J.K., K.D., H.W., J.T.), Research Center for Endocrinology and Metabolism, Göteborg University, S-405 30 Göteborg, Sweden; Institut National de la Santé et de la Recherche Médicale Unité 584 (P.A.K.), Faculté de Médecine Necker-Enfants Malades, 75730 Paris, France; and Laboratory of Cell Regulation and Carcinogenesis (J.G.), National Cancer Institute, Bethesda, Maryland 20892-1402

Address all correspondence and requests for reprints to: Dr. Christopher Ormandy, Garvan Institute of Medical Research, 384 Victoria Street Darlinghurst, New South Wales 2010, Australia. 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 investigated prostate development, gene expression, and simian virus 40 (SV40)T-induced prostate carcinogenesis 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 of 11 detected in wild-type and 4 of 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.

This article has been cited by other articles:

				P. W. Harvey, D. J. Everett, and C. J. Springall Adverse effects of prolactin in rodents and humans: breast and prostate cancer J Psychopharmacol, March 1, 2008; 22(2_suppl): 20 - 27. [Abstract] [PDF]

				N. Ben-Jonathan, C. R. LaPensee, and E. W. LaPensee What Can We Learn from Rodents about Prolactin in Humans? Endocr. Rev., February 1, 2008; 29(1): 1 - 41. [Abstract] [Full Text] [PDF]

				A. Bachelot and N. Binart Reproductive role of prolactin Reproduction, February 1, 2007; 133(2): 361 - 369. [Abstract] [Full Text] [PDF]

				N. Fujimoto, Y. Akimoto, T. Suzuki, S. Kitamura, and S. Ohta Identification of prostatic-secreted proteins in mice by mass spectrometric analysis and evaluation of lobe-specific and androgen-dependent mRNA expression. J. Endocrinol., September 1, 2006; 190(3): 793 - 803. [Abstract] [Full Text] [PDF]

				P W Harvey, D J Everett, and C J Springall Hyperprolactinaemia as an adverse effect in regulatory and clinical toxicology: role in breast and prostate cancer Human and Experimental Toxicology, July 1, 2006; 25(7): 395 - 404. [Abstract] [PDF]

				Z. Wang, G. S. Prins, K. T. Coschigano, J. J. Kopchick, J. E. Green, V. H. Ray, S. Hedayat, K. T. Christov, T. G. Unterman, and S. M. Swanson Disruption of Growth Hormone Signaling Retards Early Stages of Prostate Carcinogenesis in the C3(1)/T Antigen Mouse Endocrinology, December 1, 2005; 146(12): 5188 - 5196. [Abstract] [Full Text] [PDF]

				W. Wu, E. Ginsburg, B. K. Vonderhaar, and A. M. Walker S179D Prolactin Increases Vitamin D Receptor and p21 through Up-regulation of Short 1b Prolactin Receptor in Human Prostate Cancer Cells Cancer Res., August 15, 2005; 65(16): 7509 - 7515. [Abstract] [Full Text] [PDF]

				M. J. Naylor, S. R. Oakes, M. Gardiner-Garden, J. Harris, K. Blazek, T. W. C. Ho, F. C. Li, D. Wynick, A. M. Walker, and C. J. Ormandy Transcriptional Changes Underlying the Secretory Activation Phase of Mammary Gland Development Mol. Endocrinol., July 1, 2005; 19(7): 1868 - 1883. [Abstract] [Full Text] [PDF]

				V. Goffin, S. Bernichtein, P. Touraine, and P. A. Kelly Development and Potential Clinical Uses of Human Prolactin Receptor Antagonists Endocr. Rev., May 1, 2005; 26(3): 400 - 422. [Abstract] [Full Text] [PDF]

				A. Bartke Prolactin in the Male: 25 Years Later J Androl, September 1, 2004; 25(5): 661 - 666. [Full Text] [PDF]

				H. Li, T. J. Ahonen, K. Alanen, J. Xie, M. J. LeBaron, T. G. Pretlow, E. L. Ealley, Y. Zhang, M. Nurmi, B. Singh, et al. Activation of Signal Transducer and Activator of Transcription 5 in Human Prostate Cancer Is Associated with High Histological Grade Cancer Res., July 15, 2004; 64(14): 4774 - 4782. [Abstract] [Full Text] [PDF]