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Genistein Induces Phosphorylation of cAMP Response Element‐binding Protein in Neonatal Hypothalamus In Vivo

We investigated the effect of the phytoestrogen, genistein and 17β‐oestradiol on cAMP response element‐binding protein (CREB) phosphorylation in the neonatal female rat hypothalamus in vivo using western blot analysis and immunohistochemistry. Although CREB expression was insensitive to the compounds we tested, administration of genistein and 17β‐oestradiol induced rapid CREB phosphorylation (< 15 min) in the hypothalamus and its level remained elevated at 4 h. Quantitative immunohistochemical analysis showed that genistein and 17β‐oestradiol had no effect on CREB phosphorylation in the magnocellular subdivision of paraventricular nucleus. By contrast, genistein induced a dose‐dependent increase in CREB phosphorylation in the medial preoptic area (mPOA) and anteroventral periventricular nucleus (AVPV). Administration of 17β‐oestradiol also caused a rapid, dose‐dependent increase in CREB phosphorylation in the hypothalamus, mPOA and AVPV. These results demonstrate that genistein induces oestrogen‐like rapid action on CREB phosphorylation in the neonatal central nervous system in vivo.