The organochlorine compound mirex (dodecachlorooctahydro-1,3,4-metheno-2H-cyclobuta-CD-pentalene) induces an adaptive liver growth dependent on the hormonal status of the experimental animal. In the intact laboratory rat, mirex induces liver growth that is an expression of both cellular hyperplasia and hypertrophy. However, in rats subjected to adrenalectomy, mirex induces liver growth that is essentially hyperplastic. Corticosterone supplements given to rats subjected to adrenalectomy and treated with mirex restore the hypertrophic component of liver growth. Therefore it appears that the expression of the hypertrophic component of mirex-induced liver growth is corticosterone dependent.
To further explore the hormonal modulation of the expression of mirex-induced adaptive liver growth, rats subjected to thyroidectomy were studied. In male rats subjected to thyroidectomy, a single oral dose of mirex (100 mg/kg body wt) increased relative liver weight (liver wt/body wt × 100) by 62% within 72-hr after mirex administration. Liver growth occurred in the absence of [H]thymidine incorporation into liver DNA. Thus the observed liver growth was totally hypertrophic. However, in mirex-dosed rats subjected to thyroidectomy given twice-daily subcutaneous injections of thyroxine (5 mg/kg body wt), relative liver weight was increased by 204% of the control value within 72-hr after mirex administration, and there was a peak of [H]thymidine incorporation into liver DNA 54 hr after mirex administration. These studies suggest that the expression of hyperplasia in mirex-induced adaptive liver growth is thyroxine dependent. (HEPATOLOGY 1992;15:923–927).