17 beta -Oestradiol Stimulation of G-Proteins in Aged and Alzheimer's Human Brain: Comparison with Phytoestrogens

17 beta -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 conce...

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Veröffentlicht in:Journal of neuroendocrinology 2008-05, Vol.20 (5), p.587-596
Hauptverfasser: Jefremov, V, Rakitin, A, Mahlapuu, R, Zilmer, K, Bogdanovic, N, Zilmer, M, Karelson, E
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container_title Journal of neuroendocrinology
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creator Jefremov, V
Rakitin, A
Mahlapuu, R
Zilmer, K
Bogdanovic, N
Zilmer, M
Karelson, E
description 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 ( mu m) of 17 beta -oestradiol and phytoestrogens, genistein and daidzein, significantly (P
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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 ( mu m) of 17 beta -oestradiol and phytoestrogens, genistein and daidzein, significantly (P&lt;0.05) stimulate G-proteins ([35S]GTP gamma S binding) in the post-mortem hippocampal membranes of age-matched control women with the respective maximum effects of 28, 20 and 15% at 10 mu 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 mu m 17 beta -oestradiol produced significantly (P&lt;0.05) lower stimulation of G-proteins than in the control regions, stimulation by phytoestrogens revealed no remarkable decline. 17 beta -Oestradiol, genistein and daidzein revealed a selective effect on various G-proteins (G alpha s, G alpha o, G alpha i1 or G alpha 11 plus G beta 1 gamma 2) expressed in Sf9 cells. At a concentration of 10 mu m, 17 beta -oestradiol suppressed the H2O2 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 times and the 2.2-diphenyl-1-picrylhydrazyl free radical (DPPH times ) more than 17 beta -oestradiol did. In the frontocortical membranes of control women, the 20 mu m 17 beta -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 17 beta -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. 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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 ( mu m) of 17 beta -oestradiol and phytoestrogens, genistein and daidzein, significantly (P&lt;0.05) stimulate G-proteins ([35S]GTP gamma S binding) in the post-mortem hippocampal membranes of age-matched control women with the respective maximum effects of 28, 20 and 15% at 10 mu 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 mu m 17 beta -oestradiol produced significantly (P&lt;0.05) lower stimulation of G-proteins than in the control regions, stimulation by phytoestrogens revealed no remarkable decline. 17 beta -Oestradiol, genistein and daidzein revealed a selective effect on various G-proteins (G alpha s, G alpha o, G alpha i1 or G alpha 11 plus G beta 1 gamma 2) expressed in Sf9 cells. At a concentration of 10 mu m, 17 beta -oestradiol suppressed the H2O2 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 times and the 2.2-diphenyl-1-picrylhydrazyl free radical (DPPH times ) more than 17 beta -oestradiol did. In the frontocortical membranes of control women, the 20 mu m 17 beta -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 17 beta -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. 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Although in the hippocampus and frontal cortex of the Alzheimer's disease (AD) women's brain, 10 mu m 17 beta -oestradiol produced significantly (P&lt;0.05) lower stimulation of G-proteins than in the control regions, stimulation by phytoestrogens revealed no remarkable decline. 17 beta -Oestradiol, genistein and daidzein revealed a selective effect on various G-proteins (G alpha s, G alpha o, G alpha i1 or G alpha 11 plus G beta 1 gamma 2) expressed in Sf9 cells. At a concentration of 10 mu m, 17 beta -oestradiol suppressed the H2O2 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 times and the 2.2-diphenyl-1-picrylhydrazyl free radical (DPPH times ) more than 17 beta -oestradiol did. In the frontocortical membranes of control women, the 20 mu m 17 beta -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 17 beta -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.</abstract><doi>10.1111/j.1365-2826.2008.01696.x</doi><tpages>10</tpages></addata></record>
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title 17 beta -Oestradiol Stimulation of G-Proteins in Aged and Alzheimer's Human Brain: Comparison with Phytoestrogens
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