This Article Full Text Full Text (PDF) 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 Kindblom, J. Articles by Wennbo, H. Search for Related Content PubMed PubMed Citation Articles by Kindblom, J. Articles by Wennbo, H.

Prostate Hyperplasia in a Transgenic Mouse with Prostate-Specific Expression of Prolactin

Department of Physiology (J.K., K.D., J.T., H.W.), Göteborg University, Göteborg 405 30, Sweden; Department of Molecular Medicine (K.D.), Karolinska Institutet, Stockholm 171 77, Sweden; Department of Woman and Child Health (L.S.), Karolinska Hospital, Stockholm 171 76, Sweden; Cancer Research Program (F.R., C.O.), Garvan Institute of Medical Research, Sydney 2010, Australia; and Astrazeneca Transgenic Center (J.T.) and Integrative Pharmacology (H.W.), Astrazeneca R&D Mölndal, S-431 83 Mölndal, Sweden

Address all correspondence and requests for reprints to: Jon Kindblom, M.D., Department of Physiology, Box 434, Göteborg University, S-405 30 Göteborg, Sweden. E-mail: jon.kindblom{at}medic.gu.se.

Prolactin (PRL) is one of several polypeptide factors known to exert trophic effects on the prostate. We have previously reported a dramatic prostate enlargement with concurrent chronic hyperprolactinemia and elevated serum androgen levels in a PRL transgenic mouse (Mt-PRL) with ubiquitous expression of the transgene. To address the role of local PRL action in the prostate, a new transgenic mouse model (Pb-PRL) was generated using the prostate-specific rat probasin (Pb) minimal promoter to drive expression of the rat PRL gene. Pb-PRL transgenic males developed a significant enlargement of both the dorsolateral and ventral prostate lobes evident from 10 wk of age and increasing with age. Expression of the transgene was restricted to the prostate and detected from 4 wk of age. Low levels of transgenic rat PRL were detectable in the serum of adult Pb-PRL animals. Serum androgen levels were normal. The Pb-PRL prostate displayed significant stromal hyperplasia, ductal dilation, and focal areas of epithelial dysplasia. Quantitative analysis of prostatic tissue cellularity demonstrated a marked increase in the stromal to epithelial ratio in all lobes of Mt-PRL and Pb-PRL transgenic prostates compared with controls. Microdissections demonstrated an increased ductal morphogenesis in dorsolateral and ventral prostate lobes of Mt-PRL prostate vs. Pb-PRL and controls. In conclusion, this study indicates the ability of PRL to promote, directly or indirectly, ductal morphogenesis in the developing prostate and further to induce abnormal growth primarily of the stroma in the adult gland in a setting of normal androgen levels.

This article has been cited by other articles:

				J. Svensson, J. Kindblom, R. Shao, S. Moverare-Skrtic, M. K Lagerquist, N. Andersson, K. Sjogren, K. Venken, D. Vanderschueren, J.-O. Jansson, et al. Liver-derived IGF1 enhances the androgenic response in prostate J. Endocrinol., December 1, 2008; 199(3): 489 - 497. [Abstract] [Full Text] [PDF]

				E. Yatkin, J. Bernoulli, R. Lammintausta, and R. Santti Fispemifene [Z-2-{2-[4-(4-Chloro-1,2-diphenylbut-1-enyl)-phenoxy]ethoxy}-ethanol], a Novel Selective Estrogen Receptor Modulator, Attenuates Glandular Inflammation in an Animal Model of Chronic Nonbacterial Prostatitis J. Pharmacol. Exp. Ther., October 1, 2008; 327(1): 58 - 67. [Abstract] [Full Text] [PDF]

				S.-H. Tan and M. T Nevalainen Signal transducer and activator of transcription 5A/B in prostate and breast cancers Endocr. Relat. Cancer, June 1, 2008; 15(2): 367 - 390. [Abstract] [Full Text] [PDF]

				A. Dagvadorj, R. A. Kirken, B. Leiby, J. Karras, and M. T. Nevalainen Transcription Factor Signal Transducer and Activator of Transcription 5 Promotes Growth of Human Prostate Cancer Cells In vivo Clin. Cancer Res., March 1, 2008; 14(5): 1317 - 1324. [Abstract] [Full Text] [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]

				S.-H. Tan, A. Dagvadorj, F. Shen, L. Gu, Z. Liao, J. Abdulghani, Y. Zhang, E. P. Gelmann, T. Zellweger, Z. Culig, et al. Transcription Factor Stat5 Synergizes with Androgen Receptor in Prostate Cancer Cells Cancer Res., January 1, 2008; 68(1): 236 - 248. [Abstract] [Full Text] [PDF]

				A. Dagvadorj, S. Collins, J.-B. Jomain, J. Abdulghani, J. Karras, T. Zellweger, H. Li, M. Nurmi, K. Alanen, T. Mirtti, et al. Autocrine Prolactin Promotes Prostate Cancer Cell Growth via Janus Kinase-2-Signal Transducer and Activator of Transcription-5a/b Signaling Pathway Endocrinology, July 1, 2007; 148(7): 3089 - 3101. [Abstract] [Full Text] [PDF]

				D. Piwnica, I. Fernandez, N. Binart, P. Touraine, P. A. Kelly, and V. Goffin A New Mechanism for Prolactin Processing into 16K PRL by Secreted Cathepsin D Mol. Endocrinol., December 1, 2006; 20(12): 3263 - 3278. [Abstract] [Full Text] [PDF]

				C. Manhes, C. Kayser, P. Bertheau, B. Kelder, J. J Kopchick, P. A Kelly, P. Touraine, and V. Goffin Local over-expression of prolactin in differentiating mouse mammary gland induces functional defects and benign lesions, but no carcinoma. J. Endocrinol., August 1, 2006; 190(2): 271 - 285. [Abstract] [Full Text] [PDF]

				F E Utama, M J LeBaron, L M Neilson, A S Sultan, A F Parlow, K-U Wagner, and H Rui Human prolactin receptors are insensitive to mouse prolactin: implications for xenotransplant modeling of human breast cancer in mice. J. Endocrinol., March 1, 2006; 188(3): 589 - 601. [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]

				A. Colao, G. Vitale, A. Di Sarno, S. Spiezia, E. Guerra, A. Ciccarelli, and G. Lombardi Prolactin and Prostate Hypertrophy: A Pilot Observational, Prospective, Case-Control Study in Men with Prolactinoma J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2770 - 2775. [Abstract] [Full Text] [PDF]

				X. Xie, Z. Luo, K. M. Slawin, and D. M. Spencer The EZC-Prostate Model: Noninvasive Prostate Imaging in Living Mice Mol. Endocrinol., March 1, 2004; 18(3): 722 - 732. [Abstract] [Full Text] [PDF]

				K. Dillner, J. Kindblom, A. Flores-Morales, R. Shao, J. Tornell, G. Norstedt, and H. Wennbo Gene Expression Analysis of Prostate Hyperplasia in Mice Overexpressing the Prolactin Gene Specifically in the Prostate Endocrinology, November 1, 2003; 144(11): 4955 - 4966. [Abstract] [Full Text] [PDF]

				S. Bernichtein, C. Kayser, K. Dillner, S. Moulin, J. J. Kopchick, J. A. Martial, G. Norstedt, O. Isaksson, P. A. Kelly, and V. Goffin Development of Pure Prolactin Receptor Antagonists J. Biol. Chem., September 19, 2003; 278(38): 35988 - 35999. [Abstract] [Full Text] [PDF]

				P. Harkonen Paracrine Prolactin May Cause Prostatic Problems Endocrinology, June 1, 2003; 144(6): 2266 - 2268. [Full Text] [PDF]