Altered rat hepatic drug metabolism after implantation of a pituitary mammotropic tumor (MtT), Walker carcinosarcoma or adenocarcinoma and after removal of the MtT.

Abstract

The liver metabolism of hexobarbital and aminopyrine was studied at various times after implantation and removal of the Furth pituitary mammotropic tumor (MtT). A decrease in liver metabolism of these 2 compounds was noted 12 days after implantation of the MtT, and this decrease was maximum after 20 days of MtT growth. No decrease in hepatic microsomal protein was observed. Enlargement of adrenals, kidneys, liver and a decrease in testicular weight were noted in MtT-bearing animals. No relationship between organ weight changes and the reduction in liver metabolism was observed. Removal of the MtT produced a gradual return in liver drug metabolic enzyme activity to control levels by 16 days. The weight of liver, kidneys, adrenals and testes also returned to normal levels in animals without the MtT, and no relationship between changes in drug metabolism and organ weight was noted. Implantation of 2 tumors of nonpituitary origin, the Hilf adenocarcinoma R3230AC and the Walker carcinosarcoma 256, revealed a decrease in drug metabolism which occurred in rats with large tumors. This decrease was related to tumor mass, but no such relationship was established for animals with the MtT. Pituitary hormones produced by the MtT probably affect hepatic drug metabolism, and this accounts for a lack of similarity between the effect of this tumor on drug metabolism as compared with 2 tumors of nonpituitary origin. These time course studies with the MtT support the hypothesis that small amounts of pituitary hormones from a grossly undetectable tumor mass decreased hepatic microsomal drug metabolism in the rat. (Endocrinology88: 185, 1971)