IGF-I and Growth Hormone in Prostate Development and Prostate Cancer
Abstract
Significant progress has been made within the first year of this DOD award. We did experiments and published a paper providing evidence that insulin-like growth factor I (IGF-I) and growth hormone are both required for prostate gland development (Endocrinology 140:1984-1989, 1999). IOP-I has been implicated as a factor that may predispose one to prostate cancer. However, no specific relationship between IOF-I and prostate development or cancer in vivo has been previously established. To determine whether IGF-I was important in prostate development, we examined prostate architecture in lOP-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 quatemary branching (P<O.OOOl), indicating a specific impairment in gland structure. Administration of des(l-3)-IOF-I for 7 days partially reversed the deficit by increasing those parameters of prostate development (P<O.006). That IOF-I production probably mediates an effect of OH in this process was indicated by the observations that OH antagonist transgenic mice also had significantly impaired prostate development (P<O.00002) and that bovine OH had no independent effect on stimulating prostate development in IOF-I null animals. These data indicate that IOF-I deficiency is the proximate cause of impaired prostate development and give credence to the idea that, like testosterone, OH and lOP-I may be involved in prostate cancer growth as an extension of a normal process.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 1999
- Accession Number
- ADA387807
Entities
People
- David L. Kleinberg
Organizations
- NYU Langone Health