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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Specific binding and biological response of antiestrogens in the fetal uterus of the guinea pig.

The present data show that tamoxifen and nafoxidine compete specifically with estradiol for the estrogen receptor in the fetal uterus of the guinea pig. Furthermore, [3H]tamoxifen binds to the cytosol macromolecules of this fetal tissue at two classes of binding sites, one with a dissociation constant (Kd) of 1.8 +/- 0.4 x 10(-9) M and a concentration of specific binding sites (n) of 1800 +/- 100 fmol/mg protein, which corresponds to the same specific binding site as does estradiol, and a second class of sites with a Kd of 3.9 +/- 0.1 x 10(-10) M (617 +/- 77 fmol/mg protein), which does not bind estrogens. In another series of experiments, it was demonstrated that tamoxifen or nafoxidine injected into the mother (1 mg/kg/day for 3 consecutive days) stimulates fetal uterine weight with an intensity similar to that of estradiol but, in contrast to estradiol, the stimulatory effect of the progesterone receptor is limited. Also, it is observed that estradiol decreases by 80% the total number of specific estradiol binding sites (cytoplasmic plus nuclear). On the other hand, both tamoxifen and nafoxidine can translocate the estrogen receptors into the nucleus, but they have only a limited effect on the total number of specific binding sites of estradiol. It is concluded that the fetal uterus of the guinea pig responds to the effect of estrogens and antiestrogens.[1]


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