Effects of testosterone on the development of a sexually dimorphic neuromuscular system in ciliary neurotrophic factor receptor knockout mice

Motoneurons in the spinal nucleus of the bulbocavernosus (SNB) innervate th e perineal muscles, bulbocavernosus (BC), and levator ani (LA). Testosteron e regulates the survival of SNB motoneurons and muscles during perinatal li fe. Previous findings suggest that effects of testosterone on this system m ay be mediated by trophic factors-in particular, by a factor acting through the ciliary neurotrophic factor alpha-receptor (CNTFR alpha). To test the role of CNTFR alpha in the response of the developing SNP system to testost erone, CNTFR alpha +/+ and -/- mice were treated with testosterone propiona te (TP) or oil during late embryonic development. BC/LA muscle size and SNI B motoneuron number were evaluated on the day of birth, Large sex differenc es in PC and LA muscle size were present in newborn mice of both genotypes, but muscle volumes were reduced in CNTFR alpha -/- animals relative to sam e-sex, wild-type controls. Prenatal testosterone treatment completely elimi nated the sex difference in BC/LA muscle size in wild-type animals, and eli minated the effect of the CNTFR alpha gene deletion on muscle size in males . However, the effect of TP treatment on PC and LA muscle sizes was blunted in CNTFR alpha -/- females, SNB motoneuron number was sexually dimorphic i n oil-treated, wild-type mice. In contrast, there was no sex difference in SNB motoneuron number in oil-treated, CNTFR alpha knockout mice. Prenatal t reatment with testosterone did not increase SNB motoneuron number in CNTFR alpha -/- mice, but also did not significantly increase SNB motoneuron numb er in newborn wild-type animals. These findings confirm the absence of a se x difference in SNB motoneuron number in CNTFR alpha -/- mice. Moreover, th e CNTFR alpha gene deletion influences perineal muscle development and the response of the perineal muscles to testosterone, Prenatal TP treatment of CNTFR alpha -/- males overcomes the effects of the gene deletion on the BC and LA muscles without a concomitant effect on SNP motoneuron number. (C) 1 999 John Wiley & Sons, Inc.