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Genistein is a plant-derived estrogenic isoflavone commonly found in soy-based products such as soymilk and soy-based dietary supplements for treating menopausal symptoms, for example. Vasopressin is a neurosecretory nonapeptide synthesized primarily in neurons of the hypothalamus and secreted into the bloodstream from the posterior lobe of the pituitary. The endogenous opiate peptide beta-endorphin is synthesized both in neurons of the hypothalamus and in pituitary cells, primarily of the neurointermediate lobe. It has been reported that exposure to 17beta-estradiol or diethylstilbesterol increased the vasopressin content of the hypothalamus, and that estradiol valerate selectively damages hypothalamic beta-endorphin-containing neurons. Since little was known of the potential effects of estrogenic endocrine-disruptor compounds on hypothalamic neuropeptides, we fed Sprague-Dawley fetuses from day 7 in utero until sacrifice at postnatal day 77, with either a control diet (<1 ppm) or an experimental diet containing 25, 250, or 1250 ppm of genistein. We then conducted ELISA assays for hypothalamic content of both beta-endorphin and vasopressin immunoreactivity. Whereas there were no statistically reliable effects of dietary genistein on hypothalamic beta-endorphin content, vasopressin levels were significantly elevated in the 1250-ppm genistein group (p < 0.05). Elevated vasopressin levels may be associated with fluid balance, altered blood pressure, and cardiovascular effects. These data are consistent with the known actions of estradiol and may serve to explain our finding in a previous study that estrogenic endocrine-disruptors such as genistein increased sodium preference in rats exposed through their diet.

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