Estrogen stimulates release of secreted amyloid precursor protein from primary rat cortical neurons via protein kinase C pathway.

To investigate the mechanism of the action of estrogen, which stimulates the release of secreted amyloid precursor protein alpha (sAPP(alpha)) and decreases the generation of amyloid-beta protein (A(beta)), a dominant component in senile plaques in the brains of Alzheimer's disease patients. Experiments were carried out in primary rat cortical neurons, and Western blot was used to detect sAPP(alpha) in a culture medium and the total amount of cellular amyloid precursor protein (APP) in neurons. 17beta-Estradiol (but not 17alpha-estradiol) and beta-estradiol 6-(O-carboxymethyl) oxime: BSA increased the secretion of sAPP(alpha) and this effect was blocked by protein kinase C (PKC) inhibitor calphostin C, but not by the classical estrogen receptor antagonist ICI 182,780. Meanwhile, 17beta-estradiol did not alter the synthesis of cellular APP. The effect of 17beta-estradiol on sAPP(alpha) secretion is likely mediated through the membrane binding sites, and needs molecular configuration specificity of the ligand. Furthermore, the action of the PKC-dependent pathway might be involved in estrogen-induced sAPP(alpha) secretion.