Hypothalamic control of the male neonatal testosterone surge

Sex differences in brain neuroanatomy and neurophysiology underpin considerable physiological and behavioural differences between females and males. Sexual differentiation of the brain is regulated by testosterone secreted by the testes predominantly during embryogenesis in humans and the neonatal period in rodents. Despite huge advances in understanding how testosterone, and its metabolite oestradiol, sexually differentiate the brain, little is known about the mechanism that actually generates the male-specific neonatal testosterone surge. This review examines the evidence for the role of the hypothalamus, and particularly the gonadotropin-releasing hormone (GnRH) neurons, in generating the neonatal testosterone surge in rodents and primates. Kisspeptin-GPR54 signalling is well established as a potent and critical regulator of GnRH neuron activity during puberty and adulthood, and we argue here for an equally important role at birth in driving the male-specific neonatal testosterone surge in rodents. The presence of a male-specific population of preoptic area kisspeptin neurons that appear transiently in the perinatal period provide one possible source of kisspeptin drive to neonatal GnRH neurons in the mouse.