the naturally occurring c17 fatty acid esters of estradiol are longacting estrogens c17 fatty acid esters of estradiol are naturally occurring biosynthetic metabolites of estradiol a representative component of this family of esters estradiol17stearate was studied in order to determine the estrogenic properties of these unusual hydrophobic steroids following the classical estrogen bioassay a solution of this ester in oil was injected subcutaneously into immature rats once a day for 3 days there was little effect on the uterus on the first day after the third injection however on subsequent days a large stimulation of uterine growth occurred the course of this estrogenic effect was exactly opposite to that obtained with estradiol in order to eliminate the possibility that this effect on the time course of estrogenic stimulation was caused by increased solubility of the hydrophobic esters in the carrier oil the steroids were administered to adult ovariectomized animals in aqueous medium via a single intravenous injection the uterotrophic response to estradiol was maximal at 12 h and was completely dissipated in 4860 h estradiol17stearate produced a uterotrophic effect of twice the duration of estradiol in the immature rat aqueous intravenous injections of estradiol17stearate produced a greater uterotrophic effect than estradiol and this effect was still maximal 96 h later in addition this single injection of estradiol17stearate advanced the time of vaginal opening a marker for puberty in the female rat the mechanism of the prolonged estrogenic stimulation was investigated by studying the steroidal content of the uterus after injecting 3hestradiol and 3hestradiol17 stearate iv into immature rats at 1 and 4 h there was significantly more radioactivity in the uteri of the 3hestradiol treated animals at later times 8 h and onwards the total radioactivity in the uterus did not differ appreciably between the two groups however at these later times the amount of 3hestradiol was far greater in the uteri of animals receiving 3hestradiol17stearate consequently the prolonged estrogenic effects of the endogenous c17 fatty acid esters of estradiol are caused by the increased duration of the estrogenic signal it is hypothesized that one of the roles of the fatty acid is to protect the steroid nucleus from metabolism and thereby prolong the life of the parent c18 steroid thus the results of these experiments are consistent with the family of endogenous alkyl esters of estradiol having a physiological role as longacting estrogens