Simple biochemical method to assess progestin effects on human endometrial DNA synthesis and its application to endometrial carcinoma.
Endometria of normal histology from postmenopausal women receiving either estrogen or estrogen plus a progestin have been analyzed for nuclear estradiol receptor, epithelial DNA synthesis, isocitric dehydrogenase, and estradiol dehydrogenase activities. Epithelial DNA synthesis correlated positively with nuclear estradiol receptor and negatively with both the dehydrogenases; this result was obtained regardless of whether the enzyme activity was related to the protein or DNA content of the samples. Thus, either of the dehydrogenases might provide an index of progestin effects on proliferative activity in endometrial carcinomata. Provera administered in vivo had no effect on either dehydrogenase activity in soluble estradiol receptor-poor carcinomata, whereas both dehydrogenase activities were high in some but not all soluble estradiol receptor-rich tumors. The enzyme activities in Provera-treated tumors have been compared with those in normal epithelium and endometrium from postmenopausal women taking estrogen plus progestin. The activities of both dehydrogenases were lower in soluble estradiol receptor-rich carcinomata than in either endometrium or epithelium from estrogen plus progestin-primed, normal postmenopausal women. This may indicate suboptimal progestin effects in the patients with carcinoma, and potential reasons for this are discussed.
D004261:DNA Replication / Q000187:drug effects*; D004717:Endometrium / Q000187:drug effects*; D004960:Estradiol Dehydrogenases / Q000378:metabolism; D005260:Female; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D008593:Menopause; D011372:Progestins / Q000627:therapeutic use*; D011959:Receptors, Estradiol; D011960:Receptors, Estrogen / Q000032:analysis; D014594:Uterine Neoplasms / Q000188:drug therapy*
D011372:Progestins; D011959:Receptors, Estradiol; D011960:Receptors, Estrogen; D007521:Isocitrate Dehydrogenase; D004960:Estradiol Dehydrogenases