Cellular Bioavailability of Natural Hormones and Environmental Contaminants as a Function of Serum and Cytosolic Binding Factors

Abstract

Environmental contaminants have been reported to function as hormone mimics in various wildlife species. To investigate a potential mechanism for the interaction of contaminants with the endocrine system, we evaluated the cellular bioavailability of numerous chemicals. Hormone binding proteins from oviductal cytosol of the American alligator (Alligator mississippiensis) and yellow-bellied turtle (Trachemys scripta) were used in competitive binding assays with [³H] 17β-estradiol. Most of the environmental contaminants, and the potent, synthetic estrogen diethylstilbestrol (DES), did not interact with the cytosolic binding proteins. Among the compounds tested, o,p'-DDT and toxaphene exhibited the greatest affinity for the binding proteins. The functional consequence of the apparent lack of interaction of most contaminants with binding proteins was studied in a strain of yeast containing the human estrogen receptor (YES assay). The activation of YES with estradiol was reduced 30% in the presence of a physiological concentration (0.01 mg/mL) of human sex hormone binding globulin (SHBG), a hormone binding protein found in the blood. In contrast, the activity of DES was not inhibited by 0.01 mg/mL SHBG. Interestingly, ethinyl estradiol, a major component of contraceptives, did not appear to appreciably interact with SHBG in the YES system. Together, these data suggest that cytosolic and circulating binding proteins bind many environmental contaminants with much less affinity than native steroids. Therefore, such contaminants may be more hormonally active than previously hypothesized.

Keywords

3. Key words: binding factors contaminants endocrine disruption sex hormone binding globulin.

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