Studies on the postnatal development of responses of hepatic histidase to endocrine control

Abstract

Each of three known hormonal inducers of hepatic histidase ( l-histidine ammonia-lyase, EC 4.3.1.3), glucocorticoid, glucagon and estrogen, elicits a unique regulatory pattern during postnatal development of the rat: (1) In the male, glucocorticoid augments hepatic histidase activity during immaturity, the stage during which basal enzyme levels are low and rising; as maturity is approached and the enzyme has plateaued at its adult value, hepatic histidase becomes refractory to glucocorticoidal control. Hepatic histidase induction by adrenal corticoid also occurs in the immature female, however, thereafter there is a gradual inversion, in which glucocorticoid, by counteracting estrogenic induction of hepatic histidase, suppresses the high enzyme levels of the adult female. (2) In contrast, glucagon is capable of enhancing hepatic histidase at all postnatal stages in the male; in the intact adult female, however, glucagon also slightly suppresses this enzyme. Dibutyryl adenosine 3′,5′-monophosphate (dibutyryl cyclic AMP), administered with the inhibitor of its diesterase, theophylline, reproduces the inductive effects of glucagon. (3) Estrogen manifests yet a third developmental pattern of liver histidase regulation. During the first neonatal month, hepatic histidase is refractory to estrogenic induction, following which the liver develops competence to respond to estrogen with induced levels of the enzyme, an attribute which is maintained throughout postnatal life. Unlike estrogenic induction of hepatic histidase, which requires pituitary integrity, enhancement of this enzyme in immature animals by glucocorticoid and glucagon occurs in hypophysectomized animals. Administration of actinomycin D, cycloheximide or ethionine, each prevents induction of hepatic histidase by each of these hormones, indicating mandatory requirements for continued RNA and protein syntheses in each case. The three inducing hormones, injected at maximal dosages, are not additive, implying that certain common rate-limiting step(s), possibly transcriptional and/or translational, underly all three inductions.