17β‐Oestradiol Stimulation of G‐Proteins in Aged and Alzheimer’s Human Brain: Comparison with Phytoestrogens

The neuroprotective action of oestrogens and oestrogen‐like compounds is in the focus of basic and clinical research. Although such action has been shown to be associated with neuronal plasma membranes, the implication of G‐proteins remains to be elucidated. This study revealed that micromolar concentrations (μ m ) of 17β‐oestradiol and phytoestrogens, genistein and daidzein, significantly (P < 0.05) stimulate G‐proteins ([ 35 S]GTPγS binding) in the post‐mortem hippocampal membranes of age‐matched control women with the respective maximum effects of 28, 20 and 15% at 10 μ m . In the frontocortical membranes, the stimulation of G‐proteins did not differ significantly from that in hippocampal membranes. Although in the hippocampus and frontal cortex of the Alzheimer’s disease (AD) women's brain, 10 μ m 17β‐oestradiol produced significantly (P < 0.05) lower stimulation of G‐proteins than in the control regions, stimulation by phytoestrogens revealed no remarkable decline. 17β‐Oestradiol, genistein and daidzein revealed a selective effect on various G‐proteins (G αs , G αo , G αi1 or G α11 plus G β1γ2 ) expressed in Sf9 cells. At a concentration of 10 μ m , 17β‐oestradiol suppressed the H 2 O 2 and homocysteine stimulated G‐proteins in the frontocortical membranes of control women to a greater extent than phytoestrogens. In AD, the suppressing effect of each compound was lower than in the controls. In the cell‐free systems, micromolar concentrations of phytoestrogens scavenged OH • and the 2.2‐diphenyl‐1‐picrylhydrazyl free radical (DPPH • ) more than 17β‐oestradiol did. In the frontocortical membranes of control women, the 20 μ m 17β‐oestradiol stimulated adenylate cyclase with 20% maximal effect, whereas, in AD, the effect was insignificant. Genistein did not stimulate enzyme either in control or AD frontocortical membranes. Our data confirm that the agents stimulate G‐proteins in control and AD women's brains, although 17β‐oestradiol and phytoestrogens have similarities and differences in this respect. We suggest that, besides the ER‐dependent one, the ER‐independent antioxidant mechanism is responsible for the oestrogen stimulation of G‐proteins in the brain membranes. Both of these mechanisms could be involved in the neuroprotective signalling of oestrogens that contributes to their preventive/therapeutic action against postmenopausal neurological disorders.