The motoneurons of the spinal nucleus of the bulbocavernosus (SNB) and its target muscles, the bulbocavernosus and levator ani, form a sexually dimorphic circuit that is developmentally dependent on androgen exposure and exhibits numerous structural and functional changes in response to androgen exposure in adulthood. Castration of male adult rats causes shrinkage of SNB somata, and testosterone replacement reverses this effect, but the site at which androgen is acting to cause this change is undetermined. We exploited the X-chromosome residency of the androgen receptor (AR) gene to generate androgenized female rats that were heterozygous for the testicular feminization mutant (tfm) AR mutation and that, as a consequence of ontogenetic random X-inactivation, expressed a blend of androgen-sensitive wild-type cells and tfm-affected androgen-insensitive cells in the SNB. Chronic testosterone treatment of adult mosaics increased soma sizes only in androgen-competent wild-type SNB cells. The size of tfm-affected SNB somata in the same animals did not differ from the size of either the wild-type or tfm-affected SNB neurons in control mosaics that did not receive androgen treatment in adulthood. Because the muscle targets of the SNB are known to be uniformly androgen-sensitive in tfm mosaics, this mosaic analysis provides unambiguous evidence that androgenic effects on motoneuron soma size are mediated locally in the SNB. It is possible that the neuronal AR plays a permissive role in coordinating the actions of androgen.
Key words: mosaic; androgen; spinal nucleus of the bulbocavernosus; tfm mutation; soma size; steroid receptorsMost vertebrate motoneurons possess androgen receptors (ARs) (Pfaff, 1968;Sar and Stumpf, 1977;Kelley, 1986;Simerly et al., 1990), making them attractive models of steroidal effects on neuronal structure and function. The spinal nucleus of the bulbocavernosus (SNB), a cluster of motoneurons located in the dorsomedial aspect of lumbar segments 5 and 6, innervates the sexually dimorphic perineal muscles bulbocavernosus and levator ani (BC/LA), which participate in copulatory behavior. Adult male rats have more and larger SNB motoneurons than do females Arnold, 1980, 1981;Schroder, 1980). A perinatal surge of testosterone (T) in males rescues the BC/LA musculature from involution (Cihak et al., 1970) and inhibits apoptosis in the SNB (Nordeen et al., 1985). Exposing females to exogenous androgens during this critical period permanently masculinizes the SNB-BC/LA system (Breedlove and Arnold, 1983). The SNB critical period developmentally precedes AR expression in SNB cells (Jordan et al., 1991), and systemic androgen can rescue genetically androgen-insensitive SNB motoneurons provided that their BC/LA targets remain androgencompetent (Freeman et al., 1996). Furthermore, androgen is unable to rescue the SNB if the BC/LA muscles are treated with anti-androgen (Fishman and Breedlove, 1992) or extirpated (Kurz et al., 1992), indicating that androgen acts indirectly, via actions in the BC/LA, to rescu...
