Androgen spares androgen-insensitive motoneurons from apoptosis in the spinal nucleus of the bulbocavernosus in rats.
The spinal nucleus of the bulbocavernosus (SNB) is a sexually dimorphic motor nucleus in the rat lumbar spinal cord. The sex difference arises through the androgenic sparing of the motoneurons and their target muscles from ontogenetic cell death. Indirect evidence suggests that androgen acts on the target muscles rather than directly on SNB motoneurons to spare them from death. The testicular feminization mutation (Tfm), a defect in the androgen receptor (AR), blocks androgenic sparing of SNB motoneurons and their targets. The pattern of AR immunocytochemistry was previously found to be different in adult Tfm and wild-type rats: immunostaining was nuclear in most SNB cells of wild-type rats, but very few SNB cells display nuclear AR immunostaining in affected Tfm rats. Because the Tfm mutation is carried on the X chromosome, random X inactivation during development makes female carriers of Tfm (+/Tfm) genetic mosaics for androgen sensitivity. Tfm carriers, their wild-type sisters, and affected Tfm males were treated with perinatal testosterone and immunocytochemistry was used to detect androgen receptor in the SNB when the rats reached adulthood. Mosaic females could be distinguished from their wild-type sisters by external morphology. In such perinatally androgenized mosaics, adult SNB cells were equally divided between wild-type and Tfm genotype, as indicated by AR immunocytochemistry. In contrast, the pattern of AR immunocytochemistry in target muscles of mosaics appeared similar to that of wild-type females. These results indicate that early androgen spared both androgen-sensitive and -insensitive motoneurons from cell death, confirming a site of androgen action other than the motoneurons themselves.
Freeman
L M
LM
Department of Psychology, University of California, Berkeley 94720-1650, USA.
Watson
N V
NV
Breedlove
S M
SM
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D005260:Female; D005838:Genotype; D008297:Male; D009046:Motor Neurons / Q000187:drug effects*; D051381:Rats; D011944:Receptors, Androgen / Q000187:drug effects* / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects*
D000728:Androgens; D011944:Receptors, Androgen