A Histopathological Study of Multi-hormone Producing Proliferative Lesions in Estrogen-induced Rat Pituitary Prolactinoma

DOI Web Site 被引用文献3件 参考文献15件
  • Takekoshi Susumu
    Department of Cell Biology, Division of Host Defense Mechanism, Tokai University School of Medicine
  • Yasui Yuzo
    Department of Cell Biology, Division of Host Defense Mechanism, Tokai University School of Medicine
  • Inomoto Chie
    Department of Pathology, Tokai University School of Medicine
  • Kitatani Kanae
    Department of Cell Biology, Division of Host Defense Mechanism, Tokai University School of Medicine
  • Nakamura Naoya
    Department of Pathology, Tokai University School of Medicine
  • Osamura Robert Yoshiyuki
    Center for Diagnostic Pathology, International University of Health and Welfare Mita Hospital

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Rats with estrogen-induced prolactin-producing pituitary adenoma (E2-PRLoma) have been employed as an animal model of human PRL-producing pituitary adenoma in a large number of studies. Presently, we found that long-term administration of estrogen to SD rats resulted in the development of E2-PRLomas, some of which included multi-hormone producing nodules. We herein report results of histopathological analyses of these lesions. PRLoma models were created in female SD rats by 22 weeks or longer administration of a controlled-release preparation of estradiol at a dose of 10 mg/kg/2 weeks. Ten of the 11 PRLoma model rats had proliferative nodular lesions composed of large eosinophilic cells like gonadotrophs inside the PRLoma. These lesions were positive for PRL, TSHβ, and α subunits and were negative for GH, LHβ, ACTH, and S-100. Double immunostaining revealed that these large eosinophilic cells showed coexpression of PRL and TSHβ, PRL and α subunits, and TSHβ and α subunits. Those results clarified that long-term estrogen administration to female SD rats induced multi-hormone producing neoplastic pituitary nodules that expressed PRL, TSHβ, and α subunits. We studied these neoplastic nodules obtained by laser microdissection to acquire findings similar to those of the immuno­histochemical analysis. We consider that this animal model is useful for pathogenesis analyses and therapeutic agent development concerning human multi-hormone producing pituitary adenomas.

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