17 beta-Estradiol enhances the outgrowth and survival of neocortical neurons in culture.
Results of this investigation demonstrate that exposure to 17 beta-estradiol differentially and significantly regulates cortical nerve cell outgrowth depending on the cortical region. Parietal and occipital neurons treated with 1 nM 17 beta-estradiol showed a greater magnitude of neuronal outgrowth whereas outgrowth of temporal cortex neurons was decreased in the presence of 1 nM 17 beta-estradiol. Frontal cortex neurons showed a consistent enhancement of neuronal outgrowth that did not reach statistical significance. The dose response profile for 17 beta-estradiol regulation of the macromorphological features exhibited a bimodal dose response relationship whereas the dose response profile for 17 beta-estradiol regulation of the micromorphological features exhibited a dose response more characteristic of an inverted V-shaped function. An antagonist to the NMDA receptor antagonist, AP5, abolished the growth promoting effect of 17 beta-estradiol whereas the nuclear estrogen receptor antagonist ICI 182,780 did not. Lastly, neocortical neurons exposed to 17 beta-estradiol exhibited greater viability and survival than control neurons over a two week period. These data indicate that 17 beta-estradiol can enhance the growth and viability of select populations of neocortical neurons and that the growth promoting effects of 17 beta-estradiol can be blocked by an antagonist to the NMDA glutamate receptor and not by an antagonist to the estrogen nuclear receptor.
Brinton
R D
RD
Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles 90033, USA. rbrinton@hsc.usc.edu
Tran
J
J
Proffitt
P
P
Montoya
M
M
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D019579:Neocortex / Q000166:cytology / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists
D016194:Receptors, N-Methyl-D-Aspartate; D004958:Estradiol