Inhibition of tyrosine kinase receptor type B synthesis blocks axogenic effect of estradiol on rat hypothalamic neurones in vitro.
17-beta-estradiol (E2) increases axonal growth and tyrosine kinase receptor (Trk)B levels of male-derived hypothalamic neurones in vitro. To investigate whether the axogenic response depends on the upregulation of TrkB, we analysed neuritic growth and neuronal polarization in cultures treated with an antisense oligonucleotide against TrkB mRNA. In cultures without E2, treatment with 7.5 or 10 micro m antisense reduced TrkB levels and the percentage of neurones showing an identifiable axon; the number and length of minor processes were increased. In cultures treated with 5 micro m antisense, morphometric parameters were normal although total TrkB levels were reduced. The same dose prevented the E2-dependent increase of TrkB levels and suppressed the axogenic effect of E2. These results indicate that TrkB is necessary for normal neuronal growth and maturation and further suggest that an increase in TrkB is necessary for E2 to exert its axogenic effect in male-derived neurones.
Brito
V I
VI
Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET, Casilla de Correo 389, 5000 Córdoba, Argentina.
Carrer
H F
HF
Cambiasso
M J
MJ
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004958:Estradiol / Q000494:pharmacology*; D007031:Hypothalamus / Q000166:cytology*; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D016501:Neurites / Q000187:drug effects; D009457:Neuroglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D016376:Oligonucleotides, Antisense; D004958:Estradiol; D020813:Receptor, trkB