Estrogenic Regulation of Hepatic Histidase during Postnatal Development and Adulthood

Exploration of the regulatory factors governing the progressive augmentation of rat liver histidase during postnatal development has revealed that increased estrogen secretion during puberty is responsible for the steep rise in the activity of this hepatic enzyme characteristic of the maturing female. Ovarian ablation at 23 days of age depressed the rate of developmental rise in this enzyme to that observed in the male. 17β-Estradiol administration to such ovariectomized rats throughout the adolescent period evoked a precocious rise in hepatic histidase activity, which finally achieved adult levels of 2.5-fold those of estrogen-deprived animals. In the adult female, hepatic histidase is reversibly controlled by estrogen; the activity of this liver enzyme may be depressed upon ovariectomy and restored with 17β-estradiol administration. Progesterone, alone or in the presence of estradiol, is without effect on this enzyme. Investigation of the molecular processes which underlie the estrogenic regulation of hepatic histidase during puberty and in the adult has been initiated. Incubation in vitro of mixtures of liver homogenates from adult males and females indicates that neither dissociable enzyme activators nor inhibitors are responsible for the sexual dichotomy in the histidase activity levels observed in the adult. Administration in vivo of either l-ethionine, which inhibits protein synthesis, or actinomycin D, which blocks RNA production, suppresses both the normal developmental rise in histidase during puberty and the estrogenic enhancement of this enzyme in adults. Thus, continued protein synthesis and transcriptional activity are requisite to, and perhaps augmented elaboration of specific RNA and protein macromolecules underlie, both the developmental and hormonally induced enhancement in histidase level.