Relative mitogenic activities of various estrogens and antiestrogens.
The abilities of a variety of estrogens and antiestrogens to stimulate DNA synthesis in the prepuberal rat uterus were compared. One microgram of each compound was administered in vivo via a single intraperitoneal injection. DNA synthesis was assayed in vitro in isolated nuclei 24 h later. The relative mitogenicities of the steroidal estrogens were: 16 alpha-E2 less than 17 alpha-E2 = E3 = 16-EpiE3 less than 16 beta-E2 = 17 beta-E2. The potencies of several nonsteroidal estrogens were also tested. Indenestrol A was as potent at 17 beta-E2, whereas indanestrol and dimethylstilbestrol had weaker activities. The antiestrogens, nafoxidine and 4-hydroxytamoxifen, were both potent stimulators of DNA synthesis. The abilities of an estrogen to stimulate increases in uterine wet weight, DNA polymerase alpha activities, and DNA synthesis in uterine nuclei 24 h after injection were closely correlated. Because the magnitude of the stimulation of DNA synthesis was greatest, its measurement is the most sensitive of these assays of uterotrophic activity.
Stack
G
G
Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin, Madison 53706.
Korach
K
K
Gorski
J
J
D000818:Animals; D001834:Body Water / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004256:DNA Polymerase I / Q000378:metabolism; D004257:DNA Polymerase II / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology; D004964:Estriol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D005260:Female; D008934:Mitogens; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D013237:Stereoisomerism; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
D004965:Estrogen Antagonists; D004967:Estrogens; D004968:Estrogens, Non-Steroidal; D008934:Mitogens; D004958:Estradiol; D004256:DNA Polymerase I; D004257:DNA Polymerase II; D004964:Estriol