Estradiol receptors mediate estradiol-induced inhibition of mitochondrial Ca2+ efux in rat caudate nucleus and brain stem

Abstract

Our earlier studies found that in vitro estradiol modulates mitochondrial Ca2+ transport in discrete brain regions. Te presentstudy examined the role of estradiol receptors (ERs) in estradiol-induced inhibition of Ca2+efux from synaptosomal mitochondriaisolated from rat caudate nuclei and brain stems. Radioactively labeled CaCl2 (0.6 0.75 µCi 45CaCl2) was used for Ca2+ transportmonitoring. Te results revealed that in the presence of ER antagonist 7α,17β-[9[(4,4,5,5,5-pentafuoropentyl)sulfnyl]nonyl]estra- 1,3,5(10)-triene-3,17-diol (ICI 182,780) (1 µmol/L), the inhibitory efect of estradiol on mitochondrial Ca2+ efux was more than 60%decreased, suggesting the involvement of ER in this mode of estradiol neuromodulatory action. When particular contributions of ERαand ERβ were tested, it was found that ERβ agonist 2,3-bis (4-hydroxy phenyl)-propionitrile (10 nmol/L) inhibited Ca 2+ efux more than20%, while the inhibition with ERα agonist 4,4 ,4 -(4-propyl-[1 H]-pyrazole-1,3,5-triyl)trisphenol (10 nmol/L) was about 10%, bothcompared to the control. Both agonists demonstrated attenuation of Ca2+ efux decrease in the presence of mitochondrial Na+/Ca2+ exchanger antagonist 7-chloro-5-(2-chlorophenyl)-1,5-dihyhdro-4,1-benzothiazepin-2(3 H)-one (10 µmol/L), showing interferencewith the inhibitory action of that agent. Our results strongly indicate ERs as the mediators of estradiol-induced mitochondrial Ca2+ efux inhibition in rat caudate nucleus and brain stem synaptosomes.