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

ABSTRACT

A(11) 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 A(11) 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 A(11) DA neurons than females, particularly in the caudal portion of the A(11) 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 A(11) DA neurons and the lumbar spinal cord DA concentrations, organized by the presence of androgens early in life. The AR-dependent sex difference suggests that this system serves a sexually dimorphic function in the lumbar spinal cord.