Hormones and Behavior 30, 424–433 (1996) Article No. 0047 Androgen Spares Androgen-Insensitive Motoneurons from Apoptosis in the Spinal Nucleus of the Bulbocavernosus in Rats Louise M. Freeman,* ,1 Neil V. Watson,* ,2 and S. Marc Breedlove* , ² *Department of Psychology and †Graduate Group in Neuroscience, 3210 Tolman Hall, University of California, Berkeley, California 94720-1650 ing a site of androgen action other than the motoneurons The spinal nucleus of the bulbocavernosus (SNB) is a themselves.  1996 Academic Press sexually dimorphic motor nucleus in the rat lumbar spi- nal cord. The sex difference arises through the andro- genic sparing of the motoneurons and their target mus- cles from ontogenetic cell death. Indirect evidence sug- gests that androgen acts on the target muscles rather Neuronal death is a widespread phenomenon in the than directly on SNB motoneurons to spare them from developing central nervous system (CNS) and one of death. The testicular feminization mutation (Tfm), a de- the major factors shaping the brain. In rats, most popu- fect in the androgen receptor (AR), blocks androgenic lations of motoneurons undergo ontogenetic cell death sparing of SNB motoneurons and their targets. The pat- prenatally (Harris and McCaig, 1984; Oppenheim, tern of AR immunocytochemistry was previously found 1986); however, for motoneurons of the spinal nucleus to be different in adult Tfm and wild-type rats: immuno- of the bulbocavernosus (SNB), this apoptosis is delayed. staining was nuclear in most SNB cells of wild-type rats, The SNB is a lumbar motor nucleus that is influenced but very few SNB cells display nuclear AR immunostain- ing in affected Tfm rats. Because the Tfm mutation is by androgen during both development and adulthood. carried on the X chromosome, random X inactivation In male rats the SNB innervates two sexually dimorphic during development makes female carriers of Tfm (// striated muscles, the bulbocavernosus (BC) and levator Tfm) genetic mosaics for androgen sensitivity. Tfm carri- ani (LA), as well as the sexually monomorphic external ers, their wild-type sisters, and affected Tfm males were anal sphincter (Breedlove and Arnold, 1980; Schro ¨ der, treated with perinatal testosterone and immunocyto- 1980). A perinatal surge of testosterone in males rescues chemistry was used to detect androgen receptor in the the BC and LA muscles from degeneration (Ciha ´k, Gut- SNB when the rats reached adulthood. Mosaic females mann, and Hanzlikova ´, 1970) and also rescues some could be distinguished from their wild-type sisters by SNB motoneurons from apoptosis (Nordeen, Nordeen, external morphology. In such perinatally androgenized Sengelaub, and Arnold, 1985). Therefore, adult males mosaics, adult SNB cells were equally divided between have more and larger SNB motoneurons than do fe- wild-type and Tfm genotype, as indicated by AR immu- males (Breedlove and Arnold, 1980, 1981). Treating fe- nocytochemistry. In contrast, the pattern of AR immuno- males pups with androgen during this same critical cytochemistry in target muscles of mosaics appeared similar to that of wild-type females. These results indi- period can permanently masculinize their SNB cell cate that early androgen spared both androgen-sensitive number (Breedlove and Arnold, 1983). Male rats with and -insensitive motoneurons from cell death, confirm- the sex-linked recessive testicular feminization muta- tion (Tfm), a point mutation that renders 85 to 90% of androgen receptors (ARs) nonfunctional (Yarbrough, 1 Present address:Department of Biology, 229 Gilmer Hall, Univer- Quarmby, Simental, Joseph, Sart, Lubahn, Olsen, sity of Virginia, Charlottesville, VA 22903. French, and Wilson, 1990), have a feminine SNB 2 Present address: Department of Psychology, Simon Fraser Univer- sity, Burnaby, British Columbia V5A 1S6, Canada. (Breedlove and Arnold, 1981). Thus it seems clear that 424 0018-506X/96 $18.00 Copyright  1996 by Academic Press All rights of reproduction in any form reserved.