N-cadherin expression in motoneurons is directly regulated by androgens: a genetic mosaic analysis in rats.
We have recently reported that systemic androgens regulate adult N-cadherin (N-cad) expression in spinal motoneurons. However, the mechanism through which androgen mediates this effect remains undetermined. Androgen may act directly on motoneurons to regulate N-cad expression, or indirectly, via effects on androgen-sensitive afferent or efferent structures. Here, we describe a genetic mosaic investigation of this site-of-action indeterminacy. Following developmental random X chromosome inactivation, androgenized female rats heterozygous for the tfm androgen receptor mutation (X(WT)X(tfm)) are phenotypic mosaics of androgen-sensitive wild-type (WT) and androgen-insensitive (tfm) motoneurons. We compared steroid effects on WT and tfm cells in two sexually-dimorphic motoneuron pools, the spinal nucleus of the bulbocavernosus (SNB) and the dorsolateral nucleus (DLN), as well as a less steroid responsive motoneuron pool, the sexually monomorphic retrodorsolateral nucleus (RDLN). Independent of steroid treatment, a greater proportion of wild-type cells were N-cad immunoreactive (IR) in the DLN and RDLN. Following testosterone treatment, increased N-cad expression was observed in both cell types in the DLN, but in the SNB only the androgen-competent WT cells increased N-cad expression. Testosterone treatment did not significantly alter N-cad expression in the mosaic RDLN. The results indicate both cell autonomous and cell non-autonomous androgenic regulation of N-cad expression in spinal motoneurons.
Department of Psychology, Simon Fraser University, 8888 University Drive, Burnaby, BC, Canada, V5A 1S6.
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D000728:Androgens / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D015820:Cadherins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004303:Dosage Compensation, Genetic; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D009030:Mosaicism / Q000235:genetics*; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D009154:Mutation / Q000502:physiology*; D010641:Phenotype; D051381:Rats; D011944:Receptors, Androgen / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012447:Sacrum; D012727:Sex Characteristics; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014960:X Chromosome / Q000187:drug effects / Q000378:metabolism
D000728:Androgens; D015820:Cadherins; D011944:Receptors, Androgen