We examined the mechanism of abnormality of
thyroid hormone metabolism in Walker 256
carcinosarcoma-bearing rats. The serum levels of
thyroxine (T4), 3,5,3'-triiodothyronine (T3) and
thyroid-stimulating hormone (TSH), and the responses of serum T4 and T3 to exogenous TSH in
tumor-bearing rats on day 14 after inoculation of
tumor cells were significantly less than those in pair-fed control (PFC) rats, suggesting that the metabolic abnormality of
thyroid hormones may be caused by disorder of both peripheral and central functions, and that a certain
tumor-derived factor may be involved in this abnormality. An active factor responsible for the metabolic abnormality was found in soluble cytosol fraction (SF) of the
tumor cells. Administration of the SF to normal rats significantly reduced their serum T4 and T3 concentrations, liver
5'-deiodinase (5'-DI) activity, responsiveness of the thyroid gland to TSH and food intake compared with those of PFC rats, but, unlike the
tumor, did not reduce the serum TSH level. This biologically active factor in the SF was found to be a heat-labile
protein and specific to the
tumor. It was tentatively named
serum thyroid hormone reducing factor (
STRF).
STRF was partially purified from the SF by
ammonium sulfate fractionation and
DEAE-cellulose chromatography. Partially purified
STRF preparation significantly diminished the serum T4 and T3 concentrations and liver 5'-DI activity and food intake of normal rats compared with those of PFC rats, mimicking the changes associated with the
tumor in
tumor-bearing animals. These results suggested that abnormality of
thyroid hormone metabolism in
tumor-bearing animals may partly be caused by
STRF-mediated modulation at peripheral and thyroid gland levels. Whether
STRF actually induces
anorexia remains to be clarified.