Direction of estradiol metabolism as a control of its hormonal action--uterotrophic activity of estradiol metabolites

Endocrinology. 1977 Dec;101(6):1709-15. doi: 10.1210/endo-101-6-1709.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Estradiol / metabolism*
  • Estradiol / pharmacology
  • Estriol / pharmacology
  • Female
  • Hydroxyestrones / pharmacology
  • Kinetics
  • Organ Size / drug effects
  • Rats
  • Structure-Activity Relationship
  • Uterus / drug effects
  • Uterus / physiology*

Substances

  • Hydroxyestrones
  • Estradiol
  • Estriol