Effects of dexamethasone and indomethacin on estrogen-induced uterine growth.
Certain aspects of estrogen-induced uterine growth are reminiscent of an inflammatory response. Dexamethasone (DEX) and indomethacin (IND), two anti-inflammatory agents that interfere with arachidonic acid metabolism, were examined with respect to their effects on several growth-associated responses of the uterus to estrogen. Ovariectomized rats were given a s.c. injection of either DEX (2 mg) or IND (8 mg) immediately prior to receiving a s.c. injection of estradiol (10 micrograms). At 4 hr, DEX inhibited estrogen-stimulated uterine wet weight and ornithine decarboxylase (ODC) activity by 100% and 48%, respectively. At 24 hr, 3H-leucine incorporation into protein was inhibited 44% and 3H-thymidine incorporation into DNA was depressed 83%. Estrogen-stimulated increases in uterine protein/DNA ratio and epithelial microvilli density at 24 hr were not inhibited by DEX. IND inhibited estrogen-stimulated wet weight by 64% and 3H-thymidine incorporation into DNA by 42%, yet did not inhibit the increases in ODC activity, 3H-leucine incorporation into protein or protein/DNA ratio. These results suggest that the inflammation-like component of estrogen-induced uterine growth is mediated, at least in part, by arachidonic acid metabolites and is directed primarily toward stimulating cell division, and not cell growth.
D000818:Animals; D002369:Castration; D004247:DNA / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects; D004965:Estrogen Antagonists; D005260:Female; D007213:Indomethacin / Q000494:pharmacology*; D008871:Microvilli / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014599:Uterus / Q000187:drug effects* / Q000254:growth & development
D004965:Estrogen Antagonists; D011506:Proteins; D003907:Dexamethasone; D004247:DNA; D009955:Ornithine Decarboxylase; D007213:Indomethacin