Brain specific growth hormone receptor blockade modulates feeding in rats

The anabolic and lipolytic effects of Growth Hormone (GH) have been subject to decades of scientific investigation, therapeutic use and abuse. However, if and how GH influences energy balance specifically via its receptors (GH-R) in the CNS still remains unknown. GH may be both, transported to and expressed by the brain, and GH-Rs are located at hypothalamic circuits known to regulate food intake and energy expenditure. Recently, a specific GH-R antagonist (Pegvisomant (PGV), Pfizer) became available. Being used as an effective therapy for acromegaly, it also provides a unique tool to study action of endogenous and exogenous GH. We investigated the effects of CNS-specific GH-R blockade by PGV on energy homeostasis in rats. 32 Long Evans rats ♂ were cannulated (3. ventricle, positive angiotensin test prior to experiment). Following 72 hours of acclimation to experimental conditions, rats were injected with either PGV, GH (Norditropin, NovoNordisk) or saline (10mg/5µl, n=10–12 each group, 30min. before dark phase, 12/12h light phases). Food intake (FI), water intake (WI), spontaneous physical activity (SPA), energy expenditure (EE) and respiratory quotient (RQ) where measured using a customized 32 cage calorimeter, providing simultaneous, continuous and automated recording and analysis. A single central administration of GH in rats caused a modest increase in food intake as compared to saline treated controls, while central injection of PGV decreased food intake. Effects occurred during the first 24 hours after injection, but was not fully compensated in the 24 hours after that (GH 24h: 22.4±1.6g, GH 48h: 45.7±3.7g, saline 24h: 21.5±2.4g, saline 48h: 43.9±3.7g, PGV 24h: 18.3±2.0g, PGV 48h: 39.5±3.7g). Such single central administration of GH, PGV or saline had no significant effect on EE, RQ, SPA or WI. These results indicate that a specific blockade of endogenous GH action in the brain may decrease food intake in rats.