RESUMO
Steroid hormones are lipophilic suggesting they intercalate into the bilayer of target cell plasma membranes, potentially altering the fluidity and function of the membrane. The present study measured the effects of steroidal exposure on both phospholipid fluidity and integral protein mobility. Studies were performed on the effects of a variety of steroids on phosphatidylcholine liposomes, synaptosomal plasma membranes and sarcoplasmic reticulum membranes. Progesterone decreased the lipid fluidity, whereas testosterone had no effect on lipid movement. The estrogen, 17 beta-estradiol, an aromatised metabolite of testosterone, increased lipid mobility. In each case, the steroid action was concentration-dependent. The steroids all increased the activity of the Ca2+ ATPase of SR membrane, in keeping with their effects on this enzyme's aggregation state. The results suggest that, although lipid fluidity is a factor influencing protein activity, their mobility within the bilayer is the primary determinant of enzyme activity in the membrane for most proteins.
Assuntos
Estradiol/farmacologia , Fluidez de Membrana/efeitos dos fármacos , Progesterona/farmacologia , Testosterona/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/ultraestrutura , ATPases Transportadoras de Cálcio/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/enzimologia , Membrana Celular/metabolismo , Colesterol/metabolismo , Relação Dose-Resposta a Droga , Polarização de Fluorescência , Membranas Intracelulares/efeitos dos fármacos , Membranas Intracelulares/enzimologia , Membranas Intracelulares/metabolismo , Bicamadas Lipídicas/metabolismo , Lipossomos , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/ultraestrutura , Fosfatidilcolinas/metabolismo , Fosfatidilcolinas/fisiologia , Coelhos , Ratos , Ratos Endogâmicos , Retículo Sarcoplasmático/efeitos dos fármacos , Retículo Sarcoplasmático/metabolismo , Retículo Sarcoplasmático/ultraestrutura , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo , Sinaptossomos/ultraestruturaRESUMO
Changes in the biochemical composition of synaptosomal plasma membranes (SPM) isolated from mouse brains have been measured. The protein, phospholipid, and cholesterol contents all increased over the first 30 days of postnatal life, with the cholesterol to phospholipid molar ratio (one of the major determinants of lipid fluidity) also increasing in direct relation to the decrease in lipid fluidity. The fatty acid composition of SPM also changes with the increase in 18:0, and the decrease in 18:2, 18:3, and 22:4, in keeping with the increase in membrane order. Steroid hormones alter lipid fluidity to a greater degree in fluid membranes, indicating that the nongenomic effects of steroids will be most prevalent in membranes during the early prenatal period and for the first days following birth. The potential effects of xenobiotics on membrane fluidity are also discussed.
