The structure and function of oestrogens. VII. The use of (9,12,12-2H3)- and (11xi,12,12-2H3) oestradiol in a test of the quinone methide hypothesis for oestrogen action.
Ovariectomized mice were injected intravaginally with a physiological dose of (9,12,12-2H3)oestradiol (3), and a control group was similarly injected with (11xi,12,12-2H3)oestradiol (4). Gas-liquid chromatography/mass spectrometry (g.l.c./m.s.) analysis of the oestradiols recovered from the vaginae of the two sets of mice showed that the content and distribution of deuterium were the same as in the respective pure trideuterated oestradiols (3) and (4). This proved conclusively that the 9 alpha-hydrogen of oestradiol is not exchanged during residence in and stimulation of the vagina. It therefore appears unlikely that reversible quinone methide formation in oestradiol is the trigger mechanism for stimulation of RNA synthesis, unless a hydrogen transfer relay system permits repetitive removal and replacement of the hydrogen atom at C9 during the oxidation-reduction cycle.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004958:Estradiol / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology*; D005260:Female; D006859:Hydrogen / Q000378:metabolism; D051379:Mice; D011959:Receptors, Estradiol; D011960:Receptors, Estrogen / Q000378:metabolism*; D013268:Stimulation, Chemical; D014020:Tissue Extracts / Q000032:analysis; D014316:Tritium / Q000032:analysis; D014621:Vagina / Q000187:drug effects / Q000378:metabolism
D004967:Estrogens; D011959:Receptors, Estradiol; D011960:Receptors, Estrogen; D014020:Tissue Extracts; D014316:Tritium; D004958:Estradiol; D006859:Hydrogen