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J Svensson, Department of Internal Medicine, Research Centre for Endocrinology and Metabolism, Göteborg, SE-413 45, Sweden
J Kindblom, Department of Oncology, Sahlgrenska University Hospital, Göteborg, Sweden
R Shao, Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, Göteborg, 40530, Sweden
S Movérare-Skrtic, Department of Internal Medicine, Research Centre for Endocrinology and Metabolism, Göteborg, Sweden
M Lagerquist, Department of Internal Medicine, Research Centre for Endocrinology and Metabolism, Göteborg, Sweden
N Andersson, Department of Internal Medicine, Research Centre for Endocrinology and Metabolism, Göteborg, Sweden
K Sjögren, Department of Internal Medicine, Research Centre for Endocrinology and Metabolism, Göteborg, Sweden
K Venken, Katholieke Universiteit Leuven, Laboratory for Experimental Medicine and Endocrinology, Leuven, Belgium
D Vanderschueren, Katholieke Universiteit Leuven, Laboratory for Experimental Medicine and Endocrinology, Leuven, Belgium
J Jansson, Department of Internal Medicine, Research Centre for Endocrinology and Metabolism, Göteborg, Sweden
O Isaksson, Department of Internal Medicine, Research Centre for Endocrinology and Metabolism, Göteborg, Sweden
C Ohlsson, Department of Internal Medicine, Research Centre for Endocrinology and Metabolism, Göteborg, Sweden

Correspondence: Johan Svensson, Email: Johan.Svensson{at}medic.gu.se

Abstract

Both insulin-like growth factor-I (IGF-I) and androgens are major enhancers of prostate growth and are implicated in the development of prostate hyperplasia and cancer. The aim of the present study was to investigate if liver-derived endocrine IGF-I modulates the androgenic response in prostate.

Mice with adult, liver specific inactivation of IGF-I (LI-IGF-I-/- mice) displayed an approximately 80% reduction in serum IGF-I levels associated with decreased prostate weight compared to control mice [anterior prostate (AP) lobe -19%, p<0.05; dorsolateral prostate (DLP) lobe -35%; p<0.01; ventral prostate (VP) lobe -47%, p<0.01]. Reduced androgen receptor (AR) mRNA and AR protein levels were observed in the VP lobe (-34% and -30%, respectively, both p<0.05 vs. control mice). Analysis of prostate morphology showed reductions of both the glandular and the fibromuscular compartments of the VP and DLP lobes that were proportional to the reductions of the weights of these lobes. Immunohistochemistry revealed reduced intracellular AR immunoreactivity in the VP and DLP lobes. The non-aromatizable androgen dihydrotestosterone (DHT) increased the VP weight to a lesser extent in orchidectomized LI-IGF-I-/- mice than in orchidectomized controls (-40%, p<0.05 vs. control mice).

In conclusion, deficiency of liver-derived IGF-I reduces both the glandular and fibromuscular compartments of the prostate, decreases AR expression in prostate, and reduces the stimulatory effect of androgens on VP weight. These findings may explain, at least in part, the well-known clinical association between serum IGF-I levels and conditions with abnormal prostate growth.

This article has been cited by other articles:

				C. Ohlsson, S. Mohan, K. Sjogren, A. Tivesten, J. Isgaard, O. Isaksson, J.-O. Jansson, and J. Svensson The Role of Liver-Derived Insulin-Like Growth Factor-I Endocr. Rev., August 1, 2009; 30(5): 494 - 535. [Abstract] [Full Text] [PDF]