Dysregulation of IGF-I signaling in uterine leiomyoma

J Endocrinol. 2002 Jan;172(1):83-93. doi: 10.1677/joe.0.1720083.


IGF-I expression has been observed in human uterine leiomyomas. To examine whether autocrine IGF-I signaling plays a role in the growth of these tumors, we used an animal model of uterine leiomyoma (the Eker rat) to investigate regulation of IGF-I and the IGF-I receptor (IGF-IR) expression in tumors and normal myometrium. During the normal estrous cycle, myometrial IGF-I expression peaked on the day of proestrus when the rate of proliferation in this tissue is greatest. In leiomyomas, the expression of IGF-I was increased 7.5-fold compared with the age-matched normal tissue. The level of IGF-IR mRNA in both tumor and non-tumor tissues was found to inversely correlate with that of IGF-I. Changes observed in IGF-I signaling components correlated with the activation state of the signal-transducing protein insulin receptor substrate-1 (IRS-1). During diestrus and proestrus when IGF-I levels were increasing, tyrosine phosphorylation of IRS-1 was increased up to 5.7-fold in the normal myometrium relative to estrus, when IGF-I levels were the lowest. Additionally, IRS-1 phosphorylation was 4-fold greater in leiomyomas relative to age-matched normal myometrium. Autocrine stimulation of the IGF-IR may, therefore, play a role in regulating the normal growth of the myometrium, and dysregulation of IGF-I signaling could contribute to the neoplastic growth of uterine leiomyomas.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autocrine Communication
  • Blotting, Western
  • Cell Communication*
  • Cell Division / genetics
  • Female
  • Genes, Tumor Suppressor
  • Insulin Receptor Substrate Proteins
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Leiomyoma / metabolism*
  • Myometrium / metabolism
  • Phosphoproteins / metabolism
  • Phosphorylation
  • RNA, Messenger / analysis
  • Rats
  • Rats, Mutant Strains
  • Receptors, Somatomedin / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Tyrosine / metabolism
  • Uterine Neoplasms / metabolism*


  • IRS1 protein, human
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, rat
  • Phosphoproteins
  • RNA, Messenger
  • Receptors, Somatomedin
  • Tyrosine
  • Insulin-Like Growth Factor I