Engineered IGF-I expression induces glandular enlargement in the murine prostate

J Endocrinol. 2003 Jun;177(3):389-98. doi: 10.1677/joe.0.1770389.

Abstract

IGF-I has been implicated as a factor that may predispose one to prostate cancer and to benign prostatic hypertrophy (BPH). We established murine IGF-I transgenic mice under the control of rat probasin promoter and analysed the histology of the murine IGF-I-overexpressing prostate. Immunohistochemically, IGF-I was expressed in prostatic epithelial cells or basement membranes of the ventral, dorsal and lateral lobes in a line of IGF-I transgenic mice, but not in their control littermates. The anterior lobe did not express IGF-I. IGF-binding protein-3 (IGFBP-3), inhibitory to the mitogenic action of IGF-I, was detected in epithelial cells of prostatic ventral lobes, but not in those of the dorsal, lateral or anterior lobes of IGF-I transgenic mice. In controls, IGFBP-3 was not detected in epithelial cells of any prostatic lobe. Macroscopic prostatic size and the appearance of IGF-I transgenic mice were comparable with those of their control littermates of the same age. With a computed morphometric analysis, epithelial glands and intraglandular lumens in the prostatic lobes except the ventral lobe were smaller at 17 Months of age than at 14 Months both in IGF-I transgenic mice and controls. Glands and intraglandular lumens in the ventral prostatic lobes of IGF-I transgenic mice expressing more IGF-I protein in the prostate than controls were dense and enlarged similar to cysts compared with those of non-transgenic littermates without showing epithelial growth. Glands and lumens in the dorsal and lateral lobes of the IGF-I transgenic mice were also larger than controls at 14 and/or 17 Months of age. Glands in the anterior prostatic lobe of the IGF-I transgenic mice were not morphologically or morphometrically different from those of non-transgenic littermates. In conclusion, IGF-I transgenic mice under the control of rat probasin promoter showed more dense and enlarged epithelial glands in their prostatic ventral, dorsal and lateral lobes.

MeSH terms

  • Aging*
  • Animals
  • Blotting, Western / methods
  • Epithelial Cells / chemistry
  • Epithelial Cells / metabolism
  • Insulin-Like Growth Factor Binding Protein 3 / analysis
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism
  • Insulin-Like Growth Factor I / genetics*
  • Male
  • Mice
  • Mice, Transgenic
  • Prostate / metabolism*
  • Prostate / pathology*
  • Prostatic Hyperplasia / metabolism*
  • Prostatic Hyperplasia / pathology*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor I