Molecular Pharmacology, Vol 20, 165-171, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Hypophysial Regulation of Cadmium-Induced Depression of the Hepatic Monooxygenase System in the Rat

¹ Laboratory of Organ Function and Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709

The effect of acute cadmium treatment on the hepatic monooxygenase activities of adult rats was assessed 72 hr following a single dose of CdCl₂ (1.0 or 2.0 mg/kg); marked reduction in cytochrome P-450 contents and ethylmorphine N-demethylation activity was observed only in the males. Hypophysectomy at 50 days of age enhanced the cadmium responsiveness in the subsequent 80-day-old male and female rats, suggesting a protective effect of the pituitary against the hepatotoxic effects of cadmium in adult rats. However, hypophysectomy of male and female rats at 20 days of age abolished their hepatic cadmium responsivity in adult life. It appears that pituitary influences are required for a period between 20 and 50 days of age for the development of hepatic cadmium responsiveness. Therefore, we postulate that pituitary influences with cadmium-sensitizing and cadmiun-antagonizing properties may be functioning in both male and female rats during the pre- and postpubertal periods, respectively. Pituitary influences also altered the hepatic disposition of cadmium; however, the effects of the pituitary on hepatic cadmium responsiveness are probably not due to its effect on hepatic cadmium contents. Microsomes isolated from livers of untreated male or female rats which were either hypophysectomized or sham-operated showed similar susceptibility toward the in vitro inhibitory action of cadmium on the hepatic monooxygenase system.