Neonatal androgen-dependent sex differences in lumbar spinal cord dopamine concentrations and the number of A11 diencephalospinal dopamine neurons

Samuel S. Pappas, Chelsea T. Tiernan, Bahareh Behrouz, Cynthia L. Jordan, S. Marc Breedlove, John L. Goudreau, Keith J. Lookmgland

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


A11 diencephalospinal dopamine (DA) neurons provide the major source of DA innervation to the spinal cord. DA in the dorsal and ventral horns modulates sensory, motor, nociceptive, and sexual functions. Previous studies from our laboratory revealed a sex difference in the density of DA innervation in the lumbar spinal cord. The purpose of this study was to determine whether sex differences in spinal cord DA are androgen dependent, influenced by adult or perinatal androgens, and whether a sex difference in the number of lumbar-projecting A11 neurons exists. Adult male mice have significantly higher DA concentrations in the lumbar spinal cord than either females or males carrying the testicular feminization mutation (tfm) in the androgen receptor (AR) gene, suggesting an AR-dependent origin. Spinal cord DA concentrations are not changed following orchidectomy in adult male mice or testosterone administration to ovariectomized adult female mice. Administration of exogenous testosterone to postnatal day 2 female mice results in DA concentrations in the adult lumbar spinal cord comparable to those of males. Male mice display significantly more lumbar-projecting A11 DA neurons than females, particularly in the caudal portion of the A11 cell body region, as determined by retrograde tract tracing and immunohistochemistry directed toward tyrosine hydroxylase. These results reveal an AR-dependent sex difference in both the number of lumbar-projecting A11 DA neurons and the lumbar spinal cord DA concentrations, organized by the presence of androgens early in life. The AR-dependent sex difference suggests thyat this system serves a sexually dimorphic function in the lumbar spinal cord.

Original languageEnglish (US)
Pages (from-to)2423-2436
Number of pages14
JournalJournal of Comparative Neurology
Issue number13
StatePublished - Jul 1 2010
Externally publishedYes


  • A
  • Androgens
  • Diencephalospinal
  • Dopamine
  • Sex difference
  • Spinal cord

ASJC Scopus subject areas

  • Neuroscience(all)


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