Glucose-6-phosphate dehydrogenase. Translational regulation of synthesis and regulation of processing of the enzyme in the uterus by estradiol

12 h after intravenous administration of estradiol to ovariectomized mature rats, and 18-fold increase in the rate of synthesis of glucose-6-phosphate dehydrogenase (d-glucose-6-phosphate: NADP⁺ oxidoreductase, EC 1.1.1.49) is observed. At that time, functional mRNA pools coding for this protein are only elevated 7-fold, suggesting that estradiol may be exerting effects at a posttranscriptional level of protein synthesis. The effect of estradiol on the rate of translation of the mRNA for this enzyme was evaluated by estimating the average ribosomal transit times in control and estradiol-treated rats under in vivo conditions. Transit times for glucose-6-phosphate dehydrogenase were decreased from 4.9 min in estrogen-deprived rats to 2.0 and 3.4 min, respectively, in 12 or 24 h estradiol-treated rats. Transit times for total released proteins in the cytosol were similarly decreased from 2.3 min to 1.0 and 1.3 min in the same groups of animals. Glucose-6-phosphate dehydrogenase has pyroglutamate as its NH₂-terminus indicating that this region of the protein exists in a transient precursor form. The difference between the expected time after [³H]glutamate administration that [³H]pyroglutamate should be found in the enzyme and the observed first occurrence of [³H]pyroglutamate in the enzyme is 9, 2.5 and 4 min in control and 12 or 24 h in estradiol-treated rats, respectively. This indicates that the 'processing' or removal of an NH₂-terminal peptide from a percursor form of this enzyme is finalized after release of a glucose-6-phosphate dehydrogenase precursor from ribosomes and that the processing event is enhanced by estradiol.