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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.

Anestrus↗

Immunohistochemical analysis of estrogen receptors in cystic-endometritis-pyometra complex in the bitch.

Monoclonal antibodies to human estrogen receptor were used with an indirect immunohistochemical technique to localize in formalin-fixed, paraffin-embedded sections of the genital tract of the bitch. The presence of estrogen receptors in the uterus of dogs with cystic hyperplasia endometritis complex (CHE) was compared with normal uteri from dogs at the same stage of estrous cycle. Lower estrogen receptor expression was found in the squamous metaplastic epithelium covering the luminal surface of the endometrium from dogs with CHE than in the columnar epithelium from normal dogs. In contrast, the basal glands from uteri of CHE group dogs contained more estrogen receptor than glands from normal dogs at the same stage of estrous cycle. This was most pronounced and statistically significant in the late secretary stage of the estrous cycle. When the glands presented cystic degeneration, the estrogen receptor labeling was less pronounced. The highest estrogen receptor score was present in normal glands from dogs treated with progestins. In this group even cystic degenerated glands contained high estrogen receptor concentrations compared with those of the other groups. From this study it was concluded that the down regulation of estrogen receptor expression in the endometrial glands under the influence of rising progesterone concentrations is defective in dogs with CHE. Therefore it is suggested that the regulation of estrogen receptor expression in endometrial glands may play an important role in the pathogenesis of CHE in the bitch.

Journal Article↗