Liver-derived IGF1 enhances the androgenic response in prostate.
Artikel i vetenskaplig tidskrift, 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

Författare

Johan Svensson

Göteborgs universitet

Jon Kindblom

Göteborgs universitet

Ruijin Shao

Göteborgs universitet

Sofia Movérare-Skrtic

Göteborgs universitet

Jerker Fick

Göteborgs universitet

Niklas Andersson

Göteborgs universitet

Klara Sjögren

Göteborgs universitet

Katrien Venken

Dirk Vanderschueren

John-Olov Jansson

Göteborgs universitet

Olle Isaksson

Göteborgs universitet

Claes Ohlsson

Göteborgs universitet

The Journal of endocrinology

1479-6805 (ISSN)

Vol. 199 489-97

Ämneskategorier

Endokrinologi och diabetes

DOI

10.1677/JOE-08-0406

PubMed

18827067