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 oral 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 administration 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 Wistar or Zucker rats. The weight of uteri and ovaries increased with time of administration in Zucker rats treated with i.v. OE, but inguinal mammary gland 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. administration 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 other hand, oral administration of OE, even at higher daily doses, did not increase the circulating levels of either estrogen and, therefore, there were no significant effects on mammary gland proliferation or uterine weight. The oral administration of OE as a slimming drug, then, do not result in estrogenic side effects over a wide range of daily doses. (C) 2001 Elsevier Science Inc. All rights reserved.