Binding of estradiol to synaptosomal mitochondria: physiological significance

The subsynaptosomal distribution and specific binding of 17 beta -estradiol in vitro to mitochondria isolated from presynaptic nerve endings of female rat brain were examined. 17 beta -Estradiol is (i) distributed unequally i n synaptosomes and mitochondria posses the highest capacity to bind estradi ol with respect to the available amount of the hormone. (ii) Estradiol bind s specifically to isolated synaptosomal mitochondria. A Michaelis-Menten pl ot of specific binding was sigmoidal within a concentration range of 0.1-5 nM of added estradiol, with a saturation plateau at 3 nM. Binding of higher estradiol concentrations demonstrated an exponential Michaelis-Menten plot , indicating non-specific binding to mitochondria. V-max, and K-m for the s igmoidal-shape range were estimated as 46 +/- 6 fmol of estradiol/mg of mit ochondrial proteins and 0.46 +/- 0.07 nM free estradiol respectively. (iii) Esstradiol binding is not affected by the removal of ovaries. The results show that inhibition of Na-dependent Ca2+ efflux from mitochondria by estra diol occurs according to an affinity change of the translocator for Na+, at the same estradiol concentrations that show specific binding to mitochondr ial membranes. These data imply that physiological concentrations of estrad iol, acting on mitochondrial membrane properties, extragenomically modulate the mitochondrial, and consequently the synaptosomal content of Ca2+, and in that way exert a significant change in nerve cell homeostasis.