Uterotrophic effect of a saturated fatty acid 17-ester of estradiol-17β administered orally to juvenile rats

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Abstract:

In comparison to estradiol-17β, the naturally synthesized estradiol-17β-17-fatty acid esters are potent estrogens when administered subcutaneously. A lipophilic character of estradiol-17-esters could partially protect them from metabolic inactivation. In order to compare their relative estrogenic potency when administered orally, the uterotrophic response to different dosages (0, 2.5, 25, 250 and 2500 nmol/kg BW/day) of estradiol-17β and estradiol-17β-17-stearate was assessed in juvenile Sprague-Dawley female rats. Estrogens were administered by oral gavage once a day for 6 days. On the 7th day uterus and vagina were dissected, weighed, and examined microscopically. At 2.5 and 25 nmol/kg BW/day, no difference was detected in the uterus weight compared to control animals which received the vehicle alone (corn oil). At 250 nmol/kg BW/day, the uterotrophic response was maximal in estradiol-17β-17-stearate-treated animals (×2.40–2.70), whereas it was moderate in estradiol-17β-treated rats (×1.86) at the same dosage. This differential weight gain effect of estradiol-17β-17-stearate was correlated with typical microscopic changes in uterus and vagina. The results are in favour of a stronger estrogenic effect of orally given lipoidal estrogens compared to estradiol-17β. This could be explained by a slower but sustained absorption of estradiol-17β released from estradiol-17β-17-stearate by esterases and/or by a facilitated transfer of esters in the lymphatic circulation.

Keywords: Estradiol-17-esters; gavage; juvenile female rats; lymphatic circulation; uterotrophic effect

Document Type: Original Article

Affiliations: INRA, Lab. Xénobiotiques, BP 3, 31931 Toulouse Cedex 9, France, CIT, BP 563, 27005 Evreux Cedex, France

Publication date: May 1, 2001

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