Development of the limbic-hypothalamic cholecystokinin circuit: a model of sexual differentiation

Reproductive behavior is the final outcome of the integration of appropriate gonadal hormonal stimulation with olfactory and somatic cues by the steroid-sensitive limbic-hypothalamic neural circuit. Gonadal hormones sexually differentiate the structure and neurochemistry of this circuit during development. In adulthood, gonadal steroids continue to regulate the behavioral response of the animal through their effects on intercellular signalling in this limbic-hypothalamic circuit. Recently, the neuropeptide cholecystokinin has been demonstrated to be an important intercellular messenger, expression, distribution, levels, and receptors of which are regulated both during development and adulthood by the gonadal steroid environment. Studies on the development of sex differences using the cholecystokinin component of this circuit as a model have yielded insight into how gonadal steroids modulate the neurochemistry of the reproductively relevant limbic-hypothalamic circuit. Concentrating on this circuit and its role in reproduction, we will review the data about gonadal steroid effects on the distribution, expression, development, and physiology of cholecystokinin and its receptors.