A Histopathological Study of Multi-hormone Producing Proliferative Lesions in Estrogen-induced Rat Pituitary Prolactinoma.
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 immuno-histochemical analysis. We consider that this animal model is useful for pathogenesis analyses and therapeutic agent development concerning human multi-hormone producing pituitary adenomas.
Department of Cell Biology, Division of Host Defense Mechanism, Tokai University School of Medicine , 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
Susumu
S
Takekoshi
Department of Cell Biology, Division of Host Defense Mechanism, Tokai University School of Medicine , 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
Yuzo
Y
Yasui
Department of Pathology, Tokai University School of Medicine , 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
Chie
C
Inomoto
Department of Cell Biology, Division of Host Defense Mechanism, Tokai University School of Medicine , 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
Kanae
K
Kitatani
Department of Pathology, Tokai University School of Medicine , 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
Naoya
N
Nakamura
Center for Diagnostic Pathology, International University of Health and Welfare Mita Hospital , 1-4-3 Mita, Minato-ku, Tokyo 108-8239, Japan.
Robert Yoshiyuki
RY
Osamura
estrogen; laser capture microdissection; multi-hormone producing adenoma; prolactinoma