Possible role for insulin-like growth factor-I in the pathogenesis of cystic endometrial hyperplasia pyometra complex in the bitch

Cystic endometrial hyperplasia (CEH) is an important pathologic condition in the canine uterus and recognized as a common cause of illness and death in this species. The underlying cause and pathogenic mechanism responsible for this condition remains incompletely understood. Aberrant sex steroid hormone receptor expression in the uterus of dogs with CEH has been documented but not explained. In the dog there is an exceptionally high, progestin induced production of insulin-like growth factor-I (IGF-I) which is now generally accepted to be one of the most important growth factors with a high mitogenic effect on the uterus. Therefore, in this study the immunohistochemical staining intensity for IGF-I was compared among the uteri of 25 adult female dogs that had developed CEH and 14 healthy dogs in comparable stages of the estrus cycle. Specific staining for IGF-I was found in the cytoplasm epithelial cells and in smooth muscle cells of endometrium and myometrium. A marked increase in specific staining intensity for IGF-I was found in the surface epithelium, glandular epithelium and in the stroma of the uteri of dogs with CEH. The increase in IGF-I specific staining intensity was most prominent in the superficial endometrial stroma. Based on the known role of IGF-I in endometrial proliferation, it was concluded from the present study that high concentrations of IGF-I located in and around the epithelial cells of the endometrium in dogs with CEH, could play an important role in the development of CEH.