The
organochlorine compound mirex (dodecachloro-octahydro-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 x 100) by 62% within 72-hr after
mirex administration. Liver growth occurred in the absence of [3H]
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 [3H]
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.