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

Employing diisopropanolnitrosamine (DIPN)-induced rat thyroid tumors as an experimental model, the possible role of androgen in thyroid carcinogenesis was examined. The rate of tumer induction was higher in male than female rats. In male rats, at 15 to 20 weeks after the final DIPN iajection, the thyroid glands were remarkably enlarged and were being replaced by carcinoma tissues. Castration of male rats before DIPN irljection 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 fefnale rats. When testosterone (62.5 mg!kg) was administered to castrated male rats together with DIPN iojection, 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 iiijection 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 iajection, 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 ra£ 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 asstimption that tumor growth is stimulated by androgens through binding with the nuclear receptor of the thyrocytes.