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

In comparison to estradiol-17 beta, the naturally synthesized estradiol-17 beta -17-fatty acid esters are potent estrogens when administered subcutane ously. A lipophilic character of estradiol-17-esters could partially protec t them from metabolic inactivation. In order to compare their relative estr ogenic potency when administered orally, the uterotrophic response to diffe rent dosages (0, 2.5, 25, 250 and 2500 nmol/kg BW/day) of estradiol-17 beta and estradiol-17 beta -17-stearate was assessed in juvenile Sprague-Dawley female rats. Estrogens were administered by oral gavage once a day for 6 d ays. On the 7(th) day uterus and vagina were dissected, weighed, and examin ed microscopically. At 2.5 and 25 nmol/ kg BW/day, no difference was detect ed in the uterus weight compared to control animals which received the vehi cle alone (corn oil). At 250 nmol/kg BW/day, the uterotrophic response was maximal in estradiol-17 beta -treated animals (X2.40-2.70), whereas it was moderate in estradiol-17 beta -17-stearate rats (x 1.86) at the same dosage . This differential weight gain effect of estradiol-17 beta -17-stearate wa s correlated with typical microscopic changes in uterus and vagina. The res ults are in favour of a stronger estrogenic effect of orally given lipoidal estrogens compared to estradiol-17 beta. This could be explained by a slow er but sustained absorption of estradiol-17 beta released from estradiol-17 beta -17-stearate by esterases and/or by a facilitated transfer of esters in the lymphatic circulation.