Studies on the Effect of 2-Methyl-3-ethyl-4-phenyl-Δ 4 -cyclohexene carboxylic acid (ORF 3858) and Its p -Hydroxylated Metabolites on Uptake of 3 H-Estradiol-17β by the Uterus

Abstract

Summary

The para-hydroxy metabolites of 2-methyl-3-ethyl-4-phenyl-Δ⁴-cyclohexene carboxylic acid and known estrogens all depressed uptake of ³H-estradiol-17β into uterus but not intestine. In contrast no evidence for competition was seen with ORF 3858 and nonestrogenic compounds. Little incorporation of ORF 3858-³H was seen in target tissues, and neither estradiol-17β nor ORF 3858 competed for label uptake. Sucrose gradient centrifugation of uterine soluble fractions incubated with ³H-estradiol-17β produced a peak of radioactivity believed to be the estrogen receptor complex. Neither cholesterol nor ORF 3858 depressed this peak; in contrast, incubation with estradiol-17β or the para-hydroxy metabolites of ORF 3858 did depress the peak. Incubation of uterine soluble fractions with ORF 38S8-³H did not result in any peak of activity which could be correlated with the estrogen receptor peak. These data indicate that ORF 3858 is not estrogenic at the target tissue level, but that the para-hydroxylated metabolities are estrogenic.