Estrogen synthesis in the brain--role in synaptic plasticity and memory.
Estrogen and androgen are synthesized from cholesterol locally in hippocampal neurons of adult animals. These neurosteroids are synthesized by cytochrome P450s and hydroxysteroid dehydrogenases (HSDs) and 5alpha-reductase. The expression levels of enzymes are as low as 1/200-1/50,000 of those in endocrine organs, however these numbers are high enough for local synthesis. Localization of P450(17alpha), P450arom, 17beta-HSD and 5alpha-reductase is observed in principal glutamatergic neurons in CA1, CA3 and the dendate gyrus. Several nanomolar levels of estrogen and androgen are observed in the hippocampus. Estrogen modulates memory-related synaptic plasticity not only slowly but also rapidly in the hippocampus. Rapid action of 17beta-estradiol via membrane receptors is demonstrated for spinogenesis and long-term depression (LTD). The enhancement of LTD by 1-10nM estradiol occurs within 1 h. The density of spine is increased in CA1 pyramidal neurons within 2h after application of estradiol. The density of spine-like structure is, however, decreased by estradiol in CA3 pyramidal neurons. ERalpha, but not ERbeta, induces the same enhancement/suppression effects on both spinogenesis and LTD.
Hojo
Yasushi
Y
Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Komaba, Meguro, Tokyo 153-8902, Japan.
Murakami
Gen
G
Mukai
Hideo
H
Higo
Shimpei
S
Hatanaka
Yusuke
Y
Ogiue-Ikeda
Mari
M
Ishii
Hirotaka
H
Kimoto
Tetsuya
T
Kawato
Suguru
S
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D004967:Estrogens / Q000096:biosynthesis*; D006801:Humans; D008568:Memory; D009473:Neuronal Plasticity; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure
D004967:Estrogens