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Evidence That Insulin-Like Growth Factor I and Growth Hormone Are Required for Prostate Gland Development¹

Department of Medicine (W.R., D.L.K.), New York University School of Medicine, and the Department of Veterans Affairs Medical Center, New York, New York 10016; Genentech, Inc. (L.P.-B.), South San Francisco, California 94080; and Edison Biotechnology Institute (J.J.K.) and the Department of Biomedical Sciences, Ohio University, Athens, Ohio 47501

Address all correspondence and requests for reprints to: Dr. David L. Kleinberg, Department of Medicine, New York University School of Medicine, 550 First Avenue, New York, New York 10016. E-mail: kleind02{at}popmail.med.nyu.edu

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.

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