A cell culture model for androgen effects in motor neurons.
Androgens are known to alter the morphology, survival, and axonal regeneration of lower motor neurons in vivo. To understand better the molecular mechanisms of androgen action in neurons, we created a model system by stably expressing the human androgen receptor (AR) in motor neuron hybrid cells. Motor neuron hybrid cells express markers consistent with anterior horn cells and can be differentiated into a neuronal phenotype. When differentiated in the presence of androgen, AR-expressing cells, but not control cells, exhibit a dose-dependent change in morphology: androgen-treated cells develop larger cell bodies and broader neuritic processes while continuing to express neuronal markers. In addition, androgen promotes the survival of AR-expressing cells, but not control cells, under low-serum conditions. Our results demonstrate a direct trophic effect of androgens on lower motor neurons, mediated through the AR expressed in this population of neurons.
Brooks
B P
BP
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia 19104-6140, USA.
Merry
D E
DE
Paulson
H L
HL
Lieberman
A P
AP
Kolson
D L
DL
Fischbeck
K H
KH
D015415:Biomarkers; D018929:Cell Culture Techniques / Q000379:methods*; D002470:Cell Survival / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000235:genetics; D003470:Culture Media; D018076:DNA, Complementary; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006822:Hybrid Cells / Q000737:chemistry / Q000166:cytology* / Q000201:enzymology; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009046:Motor Neurons / Q000166:cytology* / Q000187:drug effects*; D009410:Nerve Degeneration; D016900:Neurofilament Proteins / Q000235:genetics; D010641:Phenotype; D011944:Receptors, Androgen / Q000502:physiology; D013739:Testosterone / Q000494:pharmacology*; D014162:Transfection
D015415:Biomarkers; D003470:Culture Media; D018076:DNA, Complementary; D008869:Microtubule-Associated Proteins; D016900:Neurofilament Proteins; D011944:Receptors, Androgen; D013739:Testosterone; D002795:Choline O-Acetyltransferase