Liver-derived IGF1 enhances the androgenic response in prostate.
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.
Svensson
Johan
J
Division of Endocrinology, Department of Internal Medicine, Sahlgrenska Academy, Sahlgrenska University Hospital, Göteborg University, Gröna Stråket 8, SE-413 45 Göteborg, Sweden. johan.svensson@medic.gu.se
Kindblom
Jon
J
Shao
Ruijin
R
Movérare-Skrtic
Sofia
S
Lagerquist
Marie K
MK
Andersson
Niklas
N
Sjögren
Klara
K
Venken
Katrien
K
Vanderschueren
Dirk
D
Jansson
John-Olov
JO
Isaksson
Olle
O
Ohlsson
Claes
C
D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000097:blood; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000097:blood
D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I