The Effect of the Walker 256 Carcinoma on Hepatic Δ4-Steroid Hydrogenase Activity

Abstract

THE reduction of Ring A of adrenal steroids by the A4-steroid hydrogenases of liver has been shown in man (Peterson, Wyngaarden, Guerra, Brodie and Bunim, 1958) and in the rat (Glenister and Yates, 1961) to be the rate-controlling step in the inactivation of corticosteroids. Urquhart, Yates and Herbst (1959) (Urquhart et al., 1959). These authors therefore concluded that it is the level of hepatic A4-steroid hydrogenase activity which determines adrenal size rather than the reverse.Since adrenal hypertrophy is a common feature of tumour-bearing animals (Begg, 1958) the present study was undertaken to determine whether the presence of a growing tumour affected the rate of hepatic reduction of Ring A of adrenal steroids. EXPERIMENTAL METHODS AnimalsVirgin female albino rats were fasted overnight and those weighing 140-160 g. were selected and housed in individual cages. Treatment of animalsThe animals were anaesthetised with ether and the experimental group injected intramuscularly into the right thigh with 1 ml. portions of a suspension of Walker 256 carcinoma, prepared as described by Talalay, Takano and Huggins (1952). The control group received an intramuscular injection of 1 mrnl. 0.9 per cent saline.Throughout the experimental period both groups of rats were fed a diet adequate in calories and protein content as described previously (Clark and Goodlad, 1960).The rats were killed at various time intervals after injection by stunning and exsanguination. The liver, adrenal glands and tumour were rapidly removed .znd weighed.

The Metabolism of Testosterone by Tissue From Normal and Neoplastic Rat Breast

“…A similar mechanism may apply to other steroids. The presence of implanted tumours is known to result in in¬ creased hepatic metabolism of A4-3-ketones (Goodlad & Clark, 1961 ;King & Gordon, 1963) and in increased aldosterone secretion (Millar, Davis, Toal, Brooks & White, 1962). A tumour could thus influence the steroid balance by metabolizing the steroid itself and by causing an increase in its hepatic metabolism.…”