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

摘要

Growth hormone (GH) therapy is associated with improved neurobehavior, leading to the question whether GHcrosses the blood-brain barrier (BBB) from blood after its release there from the pituitary, or whether GH exerts CNSeffects by secondary mediators, particularly insulin-like growth factor (IGF)-1. GH release from the pituitary is controllednot only by hypothalamic factors, but also by ghrelin that is mainly produced in the stomach and uses its unique structureto 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 3.8-7.6min in mouse blood and shows a slow non-saturable permeation across the BBB, with 26.8 % remaining intact in thebrain 20 min after intravenous delivery. IGF-1 crosses the BBB by saturable transport mediated by its receptors, and itsinteractions with the BBB are greatly affected by serum binding proteins. The interactions of ghrelin with the BBB appearto be dependent on species and show directionality. The BBB provides regulatory compartmentalization to fine-tune theCNS actions of GH and its related hormones.