山梨医科大学雑誌　第6巻1号　055-065(1991)

Androgen Dependent Tumorigenesis in Rat Thyroid Gland Induced by
Diisopropanolnitrosamine (DIPN) Administration

Hirotaka MATSUMOTO, Youichiro KATO, Koichi SUZUKI, and Akira KAWAOI

Abstract: Employing diisopropanolnitrosamine (DIPN)-induced rat thyroid tumors as an experimental model, the possible role of androgen in thyroid carcinogenesis was examined. The rate of tumor induction was higher in male than female rats. In male rats, at 15 to 20 weeks after the final DIPN injection, the thyroid glands were remarkably enlarged and were being replaced by carcinoma tissues. Castration of male rats before DIPN injection resulted in suppression of the occurrence of Type 2 and 3 nodules. On the other hand, no prominent difference in nodular formation was observed between gonadectomized and non-gonadectomized female rats. When testosterone (62.5 mg/kg) was administered to castrated male rats together with DlPN injection, the number of all types of nodules recovered to the levels seen in non-castrated rats. In gonadectomized female rats, administration of testosterone together with DIPN injection caused a slight increase in the number of Type 1 and 2 nodules when compared with non-gonadectomized rats. Furthermore, in male rats castrated after DIPN injection, the suppression of nodule formation was less marked in Type 2 at 15 weeks and Type 3 at 10 weeks, respectively. These findings suggest that androgens act as a stimulatory factor to the development of DIPN induced rat thyroid tumors, especially in the early stages of nodule formation. The results of an autoradiographic study using 3H-dihydrotestosterone showed that silver grains were concentrated in the nuclei of the thyrocytes, and especially in the nuclei of cells forming nodules. These observations together support the assumption that tumor growth is stimulated by androgens through binding with the nuclear receptor of the thyrocytes.

Key words: Experimental thyroid tumorigenesis, Diisopropanolnitrosamine, Autoradiography, Testosterone




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