Characterization of the Spinal Nucleus of the Bulbocavernosus Neuromuscular System in Male Mice Lacking Androgen Receptor in the Nervous System

Abstract

Motoneurons in the spinal nucleus of the bulbocavernosus (SNB) and their target bulbocavernosus (BC) and levator ani (LA) muscles play a role in male copulation and fertility. Testosterone (T) induces sexual differentiation of this SNB neuromuscular system during development and maintains its activation in adulthood. In the rat, T-induced effects mostly involve the androgen receptor (AR). However, the role of central AR in T-induced effects remains to be studied with pertinent genetic models. We addressed this question by using specific motoneuron immunolabeling and retrograde tracing in mice selectively disrupted for AR in the nervous system. This work reveals that nervous system AR is not required either for T-induced development of BC-LA muscles and perinatal sparing of SNB motoneurons from atrophy or for adult sensitivity of BC-LA muscles to T. By contrast, loss of AR expression in the nervous system resulted in SNB motoneurons having smaller somata and shorter dendrites than controls. We studied the effects of adult castration and T supplementation on SNB cell morphology in control and mutant males; these experiments showed that central AR is involved in the developmental regulation of soma size and dendritic length and in the adult maintenance of soma size of SNB motoneurons. T seemed to act indirectly through BC-LA muscles to maintain dendritic length in adulthood. Our results also suggest that central AR functions may contribute to normal activity of SNB motoneurons and perineal muscles because mutant mice displayed diminished copulatory behavior and fertility.