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Division of Endocrinology, Department of Internal Medicine, Sahlgrenska Academy, Sahlgrenska University Hospital, Göteborg University, Gröna Stråket 8, SE-413 45 Göteborg, Sweden¹ Department of Oncology, Sahlgrenska University Hospital, SE-41345 Göteborg, Sweden² Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Göteborg University, SE-40530 Göteborg, Sweden³ Laboratory for Experimental Medicine and Endocrinology, Department of Experimental Medicine, Katholieke Universiteit Leuven, Box 902, B-3000 Leuven, Belgium

(Correspondence should be addressed to J Svensson; Email: johan.svensson{at}medic.gu.se)

Both IGF1 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 whether liver-derived endocrine IGF1 modulates the androgenic response in prostate. Mice with adult, liver-specific inactivation of IGF1 (LI-IGF1^–/– mice) displayed an 80% reduction in serum IGF1 levels associated with decreased prostate weight compared with control mice (anterior prostate 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 protein levels were observed in the VP lobe (–34% and –30% respectively, both P<0.05 versus control mice). Analysis of prostate morphology showed reductions in both the glandular and fibromuscular compartments of the VP and DLP lobes that were proportional to the reductions in the weights of these lobes. Immunohistochemistry revealed reduced intracellular AR immunoreactivity in the VP and DLP lobes. The non-aromatizable androgen dihydrotestosterone increased VP weight to a lesser extent in orchidectomized (ORX) LI-IGF1^–/– mice than in ORX controls (–40%, P<0.05 versus control mice). In conclusion, deficiency of liver-derived IGF1 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 IGF1 levels and conditions with abnormal prostate growth.

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				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]