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Sex hormone binding globulin inhibits strongly the uptake of estradiol by human breast carcinoma cells via a deprivative mechanism.

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A controversy exists for many years about the role of sex hormone binding globulin (SHBG) in the uptake of estradiol by the cells. Using the estradiol-sensitive human breast carcinoma cell line MCF-7 and SHBG isolated from human serum by a new method, we observed a strong inhibition of estradiol uptake. The inhibition was higher when the concentration of the hormone was low. On the other hand, there seemed to be a lag period in inhibition when the concentrations of SHBG were very low, followed by an exponential increase, when the concentration exceeded a critical value. The inhibitory activity was higher when SHBG was added before or along with estradiol in the cell culture, as well as when the incubation period was elongated, while was dramatically minimized by the presence of dihydrotestosterone. Despite the inhibition of estradiol uptake caused by SHBG, the distribution of the hormone in various cell components remained practically the same. In conclusion, all indications from experimental data seem to suggest a simple deprivative mechanism being responsible for the inhibitory activity of SHBG on estradiol uptake by MCF-7 cells in culture.

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