Liver-derived IGF1 enhances the androgenic response in prostate.
Journal article, 2008
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 approximately 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.
metabolism
Organ Size
Immunohistochemistry
Mutant Strains
pharmacology
Prostate
Animals
Insulin-Like Growth Factor I
Androgen
drug effects
Blotting
blood
metabolism
Testosterone
physiology
genetics
Mice
drug effects
Dihydrotestosterone
metabolism
Mice
Male
Reverse Transcriptase Polymerase Chain Reaction
Estradiol
Western
Body Weight
pharmacology
blood
Receptors
drug effects
genetics
Author
Johan Svensson
University of Gothenburg
Jon Kindblom
University of Gothenburg
Ruijin Shao
University of Gothenburg
Sofia Movérare-Skrtic
University of Gothenburg
Jerker Fick
University of Gothenburg
Niklas Andersson
University of Gothenburg
Klara Sjögren
University of Gothenburg
Katrien Venken
Dirk Vanderschueren
John-Olov Jansson
University of Gothenburg
Olle Isaksson
University of Gothenburg
Claes Ohlsson
University of Gothenburg
The Journal of endocrinology
1479-6805 (ISSN)
Vol. 199 3 489-97Subject Categories
Endocrinology and Diabetes
DOI
10.1677/JOE-08-0406
PubMed
18827067