Date of Award

1972

Degree Type

Dissertation

Degree Name

Doctor of Philosophy in Pharmaceutical Sciences

Department

Interdepartmental Program

First Advisor

David R. DeFanti

Abstract

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 (Methyl-GAG) decreased uterine wet weight and partially blocked estradiol mediated alterations in uterine wet weight in animals receiving concomitant estradiol and glyoxal treatment.

The dose dependent in vitro inhibition of uterine histone acetylation is thought to occur through direct action on the ace tylation system. The I50 values reported for methylglyoxal and phenylglyoxal suggest that the drugs are equally effective as inhibitors of uterine histone acetylation.

Estradiol mediated alterations in uterine histone acetylation were characterized as a rapid depression of enzyme activity; 24 hours following hormone treatment this enzyme activity was elevated above levels . The elevation in histone acetylation following estradiol treatment was blocked by either methylglyoxal or phenylglyoxal administered 20 hours after estradiol. Uterine wet weight, total DNA, RNA/DNA and protein/DNA ratios were not affected 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 depression of uterine histone acetylation preceded the alterations in RNA/DNA and protein/DNA ratios observed 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 that the glyoxal mediated blockade of uterine histone acetylation may lead to an alteration in nucleic acid content of the hormonally stimulated uterus.

Share

COinS