A B S T R A C T A spontaneously occurring rat adrenocortical carcinoma which produces corticosterone was maintained by transplantation. The In normal adrenals, ACTH increases the activity of adenyl cyclase which catalyzes the conversion of adenosine triphosphate (ATP) to adenosine-3',5'-monophosphate (cyclic AMP), the latter then serving as an intracellular regulator of steroidogenesis. ACTH failed to increase cyclic AMP levels in the tumor in vivo or in slices in vitro, conditions under which there were 50-and 20-fold increases in nontumorous adrenals. However, in homogenates fortified with exogenous ATP, adenyl cyclase activity was comparable in the tumor and adrenals, and cyclic AMP formation was increased 3-fold by ACTH in each. As measured in homogenates, the tumor did not possess a greater ability to destroy cyclic AMP than did normal adrenals. Although ATP levels in the carcinoma were found to be considerably lower than those in normal adrenals, it was not clear that this finding can explain the inability of ACTH to increase cyclic AMP levels in intact tumor cells.While the failure to normally influence cyclic AMP levels in the carcinoma cells could be an important factor in the lack of a steroid response to ACTH, several lines of evidence suggest that the tumor possesses one or more additional abnormalities in the regulation of steroidogenesis. First, in the absence of ACTH stimulaDr. Butcher is an Investigator, Howard Hughes Medical Institute.

The rate of decrease in specific activity of blood glucose following intravenous injection of uniformly C14–labeled glucose in a series of 13 nondiabetic and 19 diabetic humans was measured over periods of 3—6 hr. In the nondiabetic humans the specific activity decreased exponentially for about 3 hr, then usually slowed down gradually over the next 3 hr. From the curves obtained up to 3 hr, rates of blood glucose replacement were estimated to be 120 mg/kg/hr, with a range of from 84 to 153 mg/kg/hr. The high and fluctuating blood glucose levels of the diabetic subjects made estimations of replacement rate somewhat uncertain, but despite a wider spread of values, the average, at 109 mg/kg/hr, was not markedly different from that of the nondiabetic subjects. Mild diabetics on the whole had a lower replacement rate, whereas severe diabetics had a markedly higher replacement rate than the normal subjects. The proportion of blood glucose carbon appearing in the respiratory CO2 was also similar—in nondiabetics, 25±3%, and in diabetics, 22 ± 5%. Despite the higher glucose pool in the diabetics, the glucose spaces were about the same at 30 ± 5% and 29 ± 3%, respectively. Taking into consideration a glucose utilization rate by brain of 60—70 mg/kg/hr, the turnover data indicate that relatively little of the glucose which enters the blood in the fasting human is used by the peripheral musculature. Submitted on November 25, 1960

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