Metabolism and biological effectiveness of di-ethylstilbestrol dicaprylate in male mice

SHIMIZU Ryosuke, INABA Toshio, IMORI Tatsuo

doi:10.1262/jrd1977.27.25

To investigate more about the long acting effect of esterified estorogen on the inhibition of gonadal activities, diethylstilbestrol dicaprylate (D₈) was synthesized and the mode of conversion from storage to effective forms of D₈ was compared with that of hexestrol dicaprylate (H₈).<BR>Estrus-inducing dose of D₈ was 20 μg for spayed rats by the vaginal smear test; a dose which was close to that of H₈. Spermatogenesis was inhibited by the injection of 0.5 mg/kg of D₈ in dogs and 15 mg/kg of D₈ in mice. Following the injection of 1.5 mg/0.2 μCi of D₈ to mice, more than 80% of the injected dose of D₈ was found at the injection site on the 30th day. Two days after the [³H]-D₈ injection, the visceral content of radioactive compounds was less than 30×10^-6 of the injected dose. In the liver, kidney, and blood, relatively high concentrations of radioactive compounds were found in the dicaprylate form. Rat uterus cytosol was incubated with either D₈, H₈, diethylstilbestrol, or hexestrol in the presence of [³H]-estradio1-17β at 4 C for 18 hours. Diethylstilbestrol and hexestrol strongly competed with [³H]-estradio1-17β for binding to cytosol estrogen receptor, while D₈ and H₈ weakly competed with it.<BR>These findings demonstrate that D₈ is absorbed slowly from the injection site and acts to the target organs after being hydrolyzed, and thus manifests long acting effect in vivo.

Metabolism and biological effectiveness of di-ethylstilbestrol dicaprylate in male mice

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