Regulation of 3-hydroxyl-3-methylglutaryl-coenzyme A reductase activity in rat uterine tissues.
Initiation of uterine DNA synthesis and mitosis in response to estrogen appears to depend upon the stimulation of protein synthesis. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase could have a key function in controlling uterine mitosis through its control of mevalonic acid and cholesterol synthesis as the rate-limiting enzyme in their synthetic pathways. These studies were initiated to examine the kinetics of the uterine increases in HMG-CoA reductase activity in response to estradiol. In the uterus of the ovariectomized mature rat, estradiol increased levels of enzyme activity in both the luminal epithelium and stroma-myometrium up to 12 h after estradiol treatment. Levels of HMG-CoA reductase activity decreased after 12 h in the luminal epithelium and further increased in the stroma-myometrium. Previous studies have shown that estradiol does not increase DNA synthesis and mitosis in the stroma-myometrium of the uterus of the ovariectomized mature rat. Since estradiol increased HMG-CoA reductase activity in both the luminal epithelium and stroma-myometrium, we conclude that even though increased HMG-CoA reductase activity may be a prerequisite for increased DNA synthesis, increases in uterine HMG-CoA reductase activity are not necessarily followed by increased DNA synthesis.
Khan
S A
SA
Department of Anatomy, University of Cincinnati, College of Medicine, OH 45267-0521.
Moulton
B C
BC
D000818:Animals; D004247:DNA / Q000096:biosynthesis; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D009215:Myometrium / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014599:Uterus / Q000187:drug effects / Q000201:enzymology*
D004958:Estradiol; D004247:DNA; D006903:Hydroxymethylglutaryl CoA Reductases