Evidence that insulin-like growth factor I and growth hormone are required for prostate gland development.
Insulin-like growth factor I (IGF-I) has been implicated as a factor that may predispose one to prostate cancer. However, no specific relationship between IGF-I and prostate development or cancer in vivo has been established. To determine whether IGF-I was important in prostate development, we examined prostate architecture in IGF-I(-/-) null mice and wild-type littermates. Glands from 44-day-old IGF-I-deficient animals were not only smaller than those from wild-type mice, but also had fewer terminal duct tips and branch points and deficits in tertiary and quaternary branching (P < 0.0001), indicating a specific impairment in gland structure. Administration of des(1-3)-IGF-I for 7 days partially reversed the deficit by increasing those parameters of prostate development (P < 0.006). That IGF-I production probably mediates an effect of GH in this process was indicated by the observations that GH antagonist transgenic mice also had significantly impaired prostate development (P < 0.0002) and that bovine GH had no independent effect on stimulating prostate development in IGF-I null animals. The data indicate that IGF-I deficiency is the proximate cause of impaired prostate development and give credence to the idea that, like testosterone, GH and IGF-I may be involved in prostate cancer growth as an extension of a normal process.
Ruan
W
W
Department of Medicine, New York University School of Medicine, and the Department of Veterans Affairs Medical Center, New York 10016, USA.
Powell-Braxton
L
L
Kopchick
J J
JJ
Kleinberg
D L
DL
D000818:Animals; D001824:Body Constitution; D001835:Body Weight; D002417:Cattle; D005260:Female; D013006:Growth Hormone / Q000037:antagonists & inhibitors / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000494:pharmacology; D011467:Prostate / Q000254:growth & development* / Q000473:pathology
D010446:Peptide Fragments; C058957:insulin-like growth factor 1, des-(1-3)-; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone