Direction of estradiol metabolism as a control of its hormonal action--uterotrophic activity of estradiol metabolites.
The uterotrophic activities of the catechol metabolites of estradiol 2-hydroxyestrone, 2-methoxyestrone and 2-hydroxyestradiol were measured under conditions of continuous administration of sc implanted paraffin pellets. The activity of these estrogens was compared to that of estradiol-17beta and its other principal metabolites estrone, estriol and 15alpha-hydroxyestriol (estetrol). The major catechol estrogens, 2-hydroxyestrone and 2-methoxyestrone, and the pregnancy metabolite, 15alpha-hydroxyestriol, exhibited no uterotrophic activity. The minor catecholestrogen, 2-hydroxyestradiol, showed some activity whose character was different from that exhibited by implants of estradiol, estrone and estriol all of which were equipotent uterotrophic agents. Implants of 2-hydroxyestrone in the presence of estradiol or estriol pellets did not diminish the response to the latter indicating that the 2-hydroxyestrone is not antiestrogenic under these conditions. It is concluded that the direction of estradiol metabolism can have a profound influence on the expression of peripheral hormonal activity with hydroxylation at C-2 terminating and hydroxylation at C-16 extending it.
D000818:Animals; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D004964:Estriol / Q000494:pharmacology; D005260:Female; D006894:Hydroxyestrones / Q000494:pharmacology; D007700:Kinetics; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship; D014599:Uterus / Q000187:drug effects / Q000502:physiology*
D006894:Hydroxyestrones; D004958:Estradiol; D004964:Estriol