Metabolic control mechanisms in mammalian systems—IX: Estrogen-like stimulation of uterine enzymes by o,p'-1,1,1-trichloro-2-2-bis (p-chlorophenyl) ethane

Abstract

The widespread occurrence of 1,1,1-trichloro-2-2-bis ( p-chlorophenyl) ethane (DDT) in our environment and the possibility that this insecticide may have adverse effects on animal fertility led us to investigate the influence of this chlorinated hydrocarbon on carbohydrate metabolism in uteri of ovariectomized rats. Administration of o, p′-DDT (10 mg/100 g) significantly enhanced uterine weights, glycogen content and the activities of hexokinase, phosphofructokinase, aldolase and pyruvate kinase as well as of glucose 6-phosphate and 6-phosphogluconate dehydrogenases. o, p′-DDT treatment, on the other hand, resulted in only minor increases in uterine aldolase, pyruvate kinase and glucose 6-phosphate dehydrogenase without exerting any appreciable effect on the other enzymes or on glycogen. Time-course studies demonstrated that, while significant increases in uterine weight and in the activities of most enzymes occurred within 4 hr after a single injection of o, p′-DDT, maximal increases were attained at 16 hr. Chronic treatment with o, p′-DDT (5.0 mg/100 g) for 3 days produced increases in uterine enzyme activities greater than those observed after a single dose of the pesticide. Administration of either actinomycin or cycloheximide to o, p′-DDT-treated animals effectively blocked the insecticide-stimulated increases in uterine glycloytic and hexose monophosphate shunt enzymes, suggesting that acceleration of the synthesis of both new RNA and protein may be associated with the observed augmented enzymatic activities. Whereas concomitant treatment with estradiol-17β and o, p′-DDT produced effects on uterine enzymes which were somewhat additive, administration of progesterone resulted in an almost complete inhibition of the insecticide-stimulated enzyme increases. The present investigation indicates that DDT analogs possess uterotrophic activity and that, analogous to the action of estrogens on uterine tissue, they are capable of inducing new synthesis of several carbohydrate-metabolizing enzymes.