Oleoyl-estrone does not have direct estrogenic effects on rats

The estrogenic effects of oleoyl-estrone (OE) administration, either though continuous i.v. infusion with osmotic minipumps or administered by daily o ral gavage, were studied. Binding of OE to human recombinant purified alpha receptors was negligible, and that of estrone (E-1) was only a fraction of 17 beta -estradiol (E-2) binding. Intravenous - but not oral - OE administ ration resulted in marked increases of both E-1 and E-2 in rat plasma, but oral OE did not induce significant changes in either plasma hormone in Wist ar or Zucker rats. The weight of uteri and ovaries increased with time of a dministration in Zucker rats treated with i.v. OE, but inguinal mammary gla nd proliferation between subcutaneous adipose tissue was even more marked. Oral administration of OE, however, did not increase either uterine weight or mammary gland proliferation, even at doses (10 mu mol.kg.d) higher than those given i.v. (3.5 mu mol/kg.d). The results indicate that i.v. administ ration of OE resulted in limited estrogenic effects mainly due to the high accumulation of E-1 giving rise to significant increases in E-2. On the oth er hand, oral administration of OE, even at higher daily doses, did not inc rease the circulating levels of either estrogen and, therefore, there were no significant effects on mammary gland proliferation or uterine weight. Th e oral administration of OE as a slimming drug, then, do not result in estr ogenic side effects over a wide range of daily doses. (C) 2001 Elsevier Sci ence Inc. All rights reserved.