Cell death and sexual differentiation of the nervous system

Sex differences in nuclear volume or neuron number often are attributed to the hormonal control of cell death. In the spinal nucleus of the bulbocavernosus, the central portion of the medial preoptic nucleus, and the principal nucleus of the bed nucleus of the stria terminalis testicular hormones decrease cell death during perinatal life, resulting in a male advantage in neuron number in adulthood. Conversely, males have more dying cells during development and fewer neurons in adulthood than do females in the anteroventral periventricular nucleus of the hypothalamus. This review discusses several limitations and unresolved issues in the literature on sexually dimorphic cell death, and identifies molecular mechanisms by which gonadal steroids may control cell survival. In particular, evidence is presented for the hormonal regulation of neurotrophic factors and involvement of Bcl-2 family proteins in the determination of sex differences in neuron number.