Anti-anxiety, cognitive, and steroid biosynthetic effects of an isoflavone-based dietary supplement are gonad and sex-dependent in rats

Isoflavone-rich diets are associated with reduced menopausal symptoms and lowered risk of cancers of reproductive tissues. Isoflavones may mimic some effects of estrogen by binding to estrogen receptors, and/or altering steroid availability. Despite their potential health benefits, neither the effects, nor mechanisms, of isoflavones are well understood. We hypothesized that isoflavones would alter behavior and physiology of rats in sex and/or gonad-dependent manner. An isoflavone-based, commercially-available, dietary supplement was administered via subcutaneous implantation to female and male, intact and gonadectomized Long–Evans rats. Affective (elevated plus-maze), cognitive (water-maze), and reproductive (sexual) behavior was examined. Weights of reproductive structures were measured, as an index of trophic effects. Steroid levels in circulation and brain regions associated with behavioral measures were evaluated by radioimmunoassay. The supplement increased anti-anxiety behavior of intact, but not gonadectomized, rats. The supplement enhanced visual–spatial performance of all rats, but this effect was most evident among proestrous female rats, which had the poorest spatial performance. There were neither effects of the supplement on sexual behavior, mass of reproductive tissues, nor plasma steroid levels. The supplement increased levels of 5α-androstane,17s-diol-3α-diol (3α-diol) in the hippocampus (but not other brain regions) of gonadectomized females. Thus, the supplement altered anxiety and cognitive behavior and brain production of steroids; however, the anti-anxiety effects were limited to rats with an intact reproductive axis and effects on cognitive performance and neurosteriodogenesis were most evident among intact and gonadectomized, female rats respectively.