Interactions of Growth Hormone, Insulin-Like Growth Factor-1, and Ghrelin with the Blood-Brain Barrier

Growth hormone (GH) therapy is associated with improved neurobehavior, leading to the question whether GH crosses the blood-brain barrier (BBB) from blood after its release there from the pituitary, or whether GH exerts CNS effects by secondary mediators, particularly insulin-like growth factor (IGF)-1. GH release from the pituitary is controlled not only by hypothalamic factors, but also by ghrelin that is mainly produced in the stomach and uses its unique structure to interact with the BBB. This review summarizes studies of the permeation of GH, IGF-1, and ghrelin across the BBB, and discusses them in the context of neuroendocrine regulation. Exogenous GH has a half-life of approximately 3.8-7.6 min in mouse blood and shows a slow non-saturable permeation across the BBB, with 26.8 % remaining intact in the brain 20 min after intravenous delivery. IGF-1 crosses the BBB by saturable transport mediated by its receptors, and its interactions with the BBB are greatly affected by serum binding proteins. The interactions of ghrelin with the BBB appear to be dependent on species and show directionality. The BBB provides regulatory compartmentalization to fine-tune the CNS actions of GH and its related hormones.