Effect of sodium fluoride on glucose-6-phosphate dehydrogenase activity in the rat uterus.
Intrauterine administration of 50 mumol of NaF to the ovariectomized mature rat causes a 2--3-fold increase in the total uterine glucose-6-phosphate dehydrogenase activity within 24 h. The response is characterized by a 4--6 h lag with a maximum effect from 24 to 36 h after a single treatment. Uterine glucose-6-phosphate dehydrogenase activity continues to increase with daily administration of NaF through 4 days. The NaF-induced response is blocked by prior intrauterine administration of cycloheximide but not actinomycin D suggesting that the enzyme activity increases by a post-transcriptional effect of NaF on de novo enzyme synthesis. Direct measurement of the effect of NaF on the rate of incorporation of [14C] leucine into immunoprecipitable uterine glucose-6-phosphate dehydrogenase indicates that NaF causes a 9-fold increase in the rate of enzyme synthesis during the interval from 12 to 16 h after treatment. The half-life of the enzyme as measured by the rate of loss of [1-14C] glutamate from previously labeled utreine glucose-6-phosphate dehydrogenase is decreased  from 27 to 10 h by NaF. The NaF response does not seem to be mediated by activation of uterine adenylyl cyclase since theophylline does not potentiate the response and since intrauterine application of cyclic AMP does not mimic the response. The increase in enzyme activity is preceded by an increase in the rate of utilization of the hexose monophosphate shunt pathway as determined by the ratio of the the rates of oxidation of [1-14C]glucose to [6-14C] glucose to CO2 by uterine slices in vitro. The action of NaF on this pathway most likely resutls from inhibition of the glycolytic enzyme, enolase, and increased pathway utilization may be the factor which controls enzyme synthesis. When given in combination with other known inducers of uterine glucose-6-phosphate dehydrogenase such as estradiol and NADP+, NaF acts synergistically.
D000818:Animals; D002369:Castration; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005459:Fluorides / Q000494:pharmacology*; D005954:Glucosephosphate Dehydrogenase / Q000096:biosynthesis / Q000378:metabolism*; D007700:Kinetics; D009249:NADP / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D013997:Time Factors; D014599:Uterus / Q000187:drug effects / Q000201:enzymology*
D004958:Estradiol; D009249:NADP; D005954:Glucosephosphate Dehydrogenase; D005459:Fluorides