Metabolic Control Mechanisms in Mammalian Systems

Abstract

The induction of phosphofructokinase by estrogenic hormones has been investigated in the uterus of the ovariectomized rat.Studies with estradiol-17@, e&one, estriol, and diethylstilbesterol revealed that estradiol-17/3 was the most potent inducer of phosphofructokinase activity.Dose response studies with estradiol-170 indicated that 1.0 pg/lOO g was sufficient to induce a statistically significant increase in enzyme activity (142 %) ; the maximum increase (391%) was observed with the 20.0-pg dose.Time course studies indicated that, following a single injection of estradiol-17& a significant rise (156%) in phosphofructokinase activity was detectable at 4 hours and reached peak levels (377%) at 16 hours.The observed increase in uterine enzyme activity was inhibited by the administration of progesterone to estradioltreated rats, although this hormone by itself exerted no significant effect.Actinomycin, puromycin, ethionine, cycloheximide, and 5fluorouracil, inhibitors of ribonucleic acid and protein synthesis, largely blocked the estrogen-induced increase in phosphofructokinase activity observed 16 hours after hormone injection.Sequential studies further showed that actinomycin, which inhibits DNA-directed synthesis of RNA, completely prevented the hormone-induced responses which occurred during 24-and 72-hour periods.The data presented suggest that the increases in uterine phosphofructokinase activity induced by estradiol-17/I represent enzyme synthesis de nouo probably involving enhanced RNA production.