Steroid hormone masculinization of neural structure in rats: a tale of two nuclei Jamie A. Johansen a , Cynthia L. Jordan a,b , S. Marc Breedlove a,b, * a Neuroscience Program, Michigan State University, East Lansing, MI 48824-1101, United States b Department of Psychology, Michigan State University, East Lansing, MI 48824-1101, United States Abstract We review the mechanisms by which steroid hormones masculinize two different regions of the central nervous system (CNS) in rats. Although in both cases, androgens induce a male phenotype, the detailed mechanisms are remarkably different in the two models. In the spinal nucleus of the bulbocavernosus (SNB), testosterone must be present during the perinatal period to spare motoneurons and their target muscles from cell death. This masculinization of the SNB system is through activation of androgen receptors, because XY rats with a defective gene for the androgen receptor fail to develop a masculine SNB system. Interestingly, the motoneurons are spared by androgen, even though they themselves do not possess androgen receptors during the critical period for their survival. Thus, steroids can act on one part of the body to secondarily masculinize the CNS. In the posterodorsal aspect of the medial amygdala (MePD), testosterone can induce masculine development even in adulthood, indicating that there is no critical period for steroids to affect sexual differentiation of this system. In the case of the MePD, both estrogen receptors and androgen receptors appear to mediate testosterone’s masculinizing influence on neural structure. The extended neural plasticity of the MePD may reflect annual breorganizationQ of the brain in the seasonally breeding ancestors of laboratory rats. D 2004 Elsevier Inc. All rights reserved. Keywords: Sexual differentiation; Androgens; Estrogens; Spinal nucleus of the bulbocavernosus; Medial amygdala In most mammalian species, the presence of a Y chromosome carrying the sex-determining region of the Y (Sry ) gene causes the fetal gonad to develop into a testis, while the absence of a Y chromosome (in XX individuals) causes the fetal gonad to develop as an ovary. Steroid secretions from the fetal testes then play a crucial role in sexual differentiation, the process by which an individual develops either a male or a female body; androgens such as testosterone masculinize internal and external structures. In females, the relative absence of testicular steroids permits the internal and external genitalia to take the feminine configuration. The process by which individuals develop either a male or female body, sexual differentiation, is thus driven by testicular secretions that organize masculine development. Over 40 years ago, Phoenix et al. [1] proposed that the same steroidal signals that masculinize the structure of external genitalia may also organize the structure of the brain and thereby masculinize behavior. This conjecture has been amply confirmed. They further speculated that just as the genitalia must be exposed to androgen in early development to be fully masculinized (androgen treatment in adulthood has only very modest effects), the brain, too, may be sensitive to the masculinizing effects of steroids only during development. Here, we will review two model systems in the central nervous system (CNS) that are masculinized by testoster- one. One model, based in the spinal cord, conforms to the original notion of steroidal organization of the nervous system: Perinatal androgen permanently alters the number of neurons present. The other model, based in the brain, is also masculinized by androgen, but the system appears to be 0031-9384/$ - see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.physbeh.2004.08.016 * Corresponding author. Neuroscience Program, 108 Giltner Hall, Michigan State University, East Lansing, MI 48824-1101, United States. Tel.: +1 517 355 1749; fax: +1 517 432 2744. E-mail address: breedsm@msu.edu (S.M. Breedlove). Physiology & Behavior 83 (2004) 271 – 277