Dietary Exposure to Genistein Increases Vasopressin but Does Not Alter beta-Endorphin in the Rat Hypothalamus

Abstract

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.

High-soy diet decreases infarct size after permanent middle cerebral artery occlusion in female rats

“…In the brain, soy diets and isolated phytoestrogens can also mimic estrogen's transcriptional actions. Soy isoflavones increase brain-derived neurotropic factor (41) and choline acetyl transferase (40) mRNA levels in the frontal cortex and increase vasopressin levels in the hypothalamus (47). Phytoestrogens can also mimic estrogen's neuroprotective effects.…”

Endocrine Disruption of Vasopressin Systems and Related Behaviors

“…Similarly, male rats maintained on a diet containing 150 µg/g GEN and daidzein displayed increased anxiety and elevated stress-induced plasma AVP and corticosterone levels (71). Elevated hypothalamic AVP content (measured by ELISA) has also been reported in rats maintained on a diet containing 1,250 ppm GEN (73). Sexually dimorphic AVP-ir in the rodent brain can also be altered by early-life exposure to GEN, including at doses akin to the levels found in soy infant formula.…”

The pros and cons of phytoestrogens

“…Similarly, male rats maintained on a diet containing 150 µg/g genistein and daidzein displayed increased anxiety and elevated stress-induced plasma vasopressin and corticosterone levels [98]. Elevated hypothalamic vasopressin has also been reported in rats fed a diet containing 1250 ppm genistein across the lifespan [236]. Anxiolytic effects of phytoestrogen-rich diets have also been reported in gonadally intact male and female rats exposed over their entire lifetimes but not when administered briefly in adulthood [145].…”