oleoyl-estrone and estrone-sulfate

Two different oral doses of oleoyl-estrone: 1 and 10 nmol/g a day were given once to male Wistar rats. The serum levels of free estrone, estrone sulphate, estradiol, and acyl-estrone were measured at intervals up to 72 h after the gavage. Oleoyl-estrone was rapidly absorbed; with the 1 nmol/g dose no changes were observed in plasma acyl-estrone but levels increased dramatically with 10 nmol/g, peaking at 6 h; high acyl-estrone levels were maintained up to 24 h, returning to normalcy at 48 h. With the 10 nmol/g dose, free estrone at most doubled its levels but estrone sulphate concentrations rose by one order of magnitude; in both cases, the increases soon (2 h) reached a plateau that was maintained for almost two days. Estradiol levels remained unchanged except for a transient peak at 2 h at the 10 nmol/g dose. The relationship between free estrone and its sulphate was linear, and those of estrone and estrone sulphate versus acyl-estrone showed the existence of an upper serum concentration limit for both molecules. The results hint at estrone sulphate being an important metabolite of oleoyl-estrone disposal, confirm the limited estrogenic response to oleoyl-estrone administration and agree with a rapid absorption and disposal of oleoyl-estrone, nevertheless maintaining high circulating levels of the ester for a time after its oral administration.

Topics: Administration, Oral; Animals; Anti-Obesity Agents; Estradiol; Estrone; Male; Oleic Acids; Rats; Rats, Wistar

Oleoyl-estrone is a powerful, slimming adipose tissue-derived signal that has biological effects widely opposed to those of its estrone moiety. The present experiment was designed to determine whether oleoyl-estrone effects on body energy are mediated by the estrogen receptor, blocked with the antagonist tamoxifen. Male Wistar rats were given daily oral doses of 10 micromol/kg d of oleoyl-estrone in oil containing 0 or 0.40 mg/kg d of tamoxifen. The data were compared with controls receiving only oil or 50 nmol/kg d of free estrone. After 10 days, the rats were killed, and their body composition and plasma metabolites and hormones were analyzed. Rats receiving estrone increased their body energy and lipid content compared with controls. Both groups of oleoyl-estrone-treated rats lost body weight, energy, and lipid; the losses in the rats receiving tamoxifen alone were less marked than in those receiving oleoyl-estrone. No significant changes in plasma glucose or triacylglycerols were observed. The patterns of change of estrone sulphate, estradiol, and oleoyl-estrone were consistent with a noticeable hydrolysis of oleoyl-estrone. The lack of differences in the fat mass in oleoyl-estrone-treated rats irrespective of the presence of tamoxifen suggested that the estrogenic pathway was not responsible for the slimming effects observed. Thus, it can be concluded that oleoyl-estrone effects are not mediated through its conversion to estrone or estradiol acting through the estrogen receptor. Tamoxifen partly mimicked the slimming effects of oleoyl-estrone; this could be speculatively explained by tamoxifen acting through the oleoyl-estrone signalling pathway.

Topics: Animals; Anti-Obesity Agents; Blood Glucose; Body Composition; Body Weight; Energy Intake; Energy Metabolism; Estradiol; Estrogen Antagonists; Estrone; Lipid Mobilization; Male; Oleic Acids; Rats; Rats, Wistar; Receptors, Estrogen; Tamoxifen; Triglycerides