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Procaccini, Robe rt Louis. Ph.D., University of Rhode Island, June , 1972. Glyoxal and Estradiol Mediated Alterations in Rat Uterine Histone Acetylation. Major Professor: Dr. David R. DeFanti. The immature rat uterus was developed as a model in which to measure alterations in his tone acetylation in a target organ following hormonal stimulation. The effect of various glyoxal derivatives on his tone acetylation and several other parameters was measured in the uterine tissue of untreated and estradiol treated animals. Six day treatment with glyoxal monohydrate and methylglyoxal-bis-guanyl hydrazone (Me thyl-GAG) decreased uterine wet weight and par tially blocked e stradiol m.edi ated alterations in uterine vvet weight in animals r eceiving concomitant e stradiol and glyoxal treatment. The dose dependent in vitro inhibition of uterine histone acetylation is thought to oc cur through direct action on the ace tyl ation system.. Th e 1 50 values reported for methylglyoxal and phenylglyoxal suggest that the dru gs are equally effective as inhibitors of uterine histone acetylation. Estradiol mediated alterations in uterine histone acetylation were characterized as a r apid depression of enzyme activity; 24 hours following horn1onc treatme nt thi s enz yme activity was el8vatcd above control l eve l s . The elevation in his tone ace tylation following estradiol treatment wa .s bloc ked by eiLli.er methyJglyoxa l or ph'"~nylglyoxal administc1·ed 20 hour~ afi:cr est~aciol. Ut.erine \\·c l· \veight, total DNA, RNA/DNA and protein/DNA ratios were not affe cted by this treatment. These data suggest that histone acetylation may not be of primary importance in estradiol stimulation of the rat uterus. The phenylglyoxal mediated depressio-n of uterine histone acetylation preceded the alterations in RNA/DNA and prote in/DNA ratios obs erved when phenylglyoxal pretreatment was extended to 48 hours. Elevations in total DNA and protein/DNA ratios in the uterus of estradiol treated rats were partially suppressed in animals pretreated with phenylglyoxal, whereas the RNA/DNA ratio was not affected in these animals. Results from this study suggest tha t the glyoxal mediated blockade of uterine histo ne acetylation ina. y lead to an alteration in nucleic acid content of the hormonally stimulated uterus.

GLYOXAL AND ESTRADIOL MEDIATED ALTERATIONS IN RAT UTERINE HISTONE ACETYLATION