Oestrogen regulates sympathetic neurite outgrowth by modulating brain derived neurotrophic factor synthesis and release by the rodent uterus

D. Krizsan-Agbas, T. Pedchenko, Wohaib Hasan, P. G. Smith

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Sympathetic innervation of the adult rodent uterus undergoes cyclic remodelling. Terminal sympathetic axons degenerate when oestrogen levels rise and regenerate when oestrogen levels decline. This study examined the role of neurotrophins in oestrogen-mediated uterine sympathetic nerve remodelling. Oestrogen injection of ovariectomized female rats did not affect uterine NT-3 levels 24 h postinjection, and increased endometrial NGF protein, indicating that reduced NGF or NT-3 is not responsible for the oestrogen-induced denervation. Oestrogen also raised BDNF protein and mRNA in myometrium and endometrium. To assess whether increased BDNF affects uterine receptivity to sympathetic outgrowth, sympathetic ganglion explants were co-cultured with myometrium. Myometrium from ovariectomized rats induced neuritogenesis in oestrogen-free conditions, and this was abolished when BDNF was added to the medium. Neuritogenesis induced by ovariectomized myometrium was suppressed by oestrogen, and restored by a BDNF function-blocking antibody. To determine if target BDNF synthesis is required for oestrogen to suppress sympathetic neurite outgrowth, uteri from wild-type mice and mice homozygous or heterozygous for recombinant mutations of the BDNF gene were cultured with rat sympathetic ganglia. Neuritogenesis induced by wild-type uteri was diminished by oestrogen. Neurite formation in the presence of homozygous BDNF mutant uteri was not affected by oestrogen, but was lower than that of wild-type mice. Uteri from mice heterozygous for the BDNF mutation, who have reduced BDNF synthesis, showed normal neuritogenic properties, but were not affected by oestrogen. These findings suggest that oestrogen alters neuritogenic properties of the rodent uterus by regulating BDNF synthesis, which inhibits sympathetic neurite outgrowth.

Original languageEnglish (US)
Pages (from-to)2760-2768
Number of pages9
JournalEuropean Journal of Neuroscience
Volume18
Issue number10
DOIs
StatePublished - Nov 2003
Externally publishedYes

Fingerprint

Brain-Derived Neurotrophic Factor
Uterus
Rodentia
Estrogens
Myometrium
Sympathetic Ganglia
Nerve Growth Factor
Neuronal Outgrowth
Mutation
Blocking Antibodies
Presynaptic Terminals
Nerve Growth Factors
Denervation
Neurites
Endometrium
Proteins

Keywords

  • Mouse
  • Nerve degeneration
  • Neurotrophins
  • Rat

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Oestrogen regulates sympathetic neurite outgrowth by modulating brain derived neurotrophic factor synthesis and release by the rodent uterus. / Krizsan-Agbas, D.; Pedchenko, T.; Hasan, Wohaib; Smith, P. G.

In: European Journal of Neuroscience, Vol. 18, No. 10, 11.2003, p. 2760-2768.

Research output: Contribution to journalArticle

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