Genistein induces phosphorylation of cAMP response element-binding protein in neonatal hypothalamus in vivo.

We investigated the effect of the phytoestrogen, genistein and 17beta-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 17beta-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 17beta-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 17beta-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.

Sex differences in oestrogen-induced p44/42 MAPK phosphorylation in the mouse brain in vivo.

In addition to the classical direct genomic mechanisms of action, oestrogen also exerts poorly understood, nonclassical effects on the signalling system in neurones. In the present study, we investigated whether sex differences exist in gonadectomy- and oestrogen-induced effects on p44/42 mitogen-activated protein kinase (MAPK) phosphorylation in specific brain regions of mice. We demonstrate that MAPK immunoreactivity was not altered by gonadectomy or oestrogen treatment in either sex. However, we show that the level of phosphorylated MAPK (pMAPK) within the anteroventral periventricular nucleus (AVPV) was consistently higher in males than females irrespective of gonadal steroid hormone status. In addition, gonadectomy was found to decrease pMAPK immunoreactivity within the piriform cortex of males. Oestrogen increased pMAPK immunoreactivity in the medial preoptic area and AVPV of females, but failed to have the same effect in male mice. Overall, these results demonstrate a marked sex difference in oestrogen-induced alteration of MAPK phosphorylation in the brain in vivo.