Our research team investigates the neural circuits and molecular mechanisms through which the growth hormone secretagogue receptor (GHSR) acts in the brain.
GHSR is a G protein-coupled receptor highly expressed in the brain. GHSR controls a wide variety of functions including growth hormone secretion, glucose homeostasis, food intake, reward for palatable foods, stress response, autonomic nervous system activity, etc. Endogenous GHSR ligands include: ghrelin, an octanoylated peptide produced primarily in the gastrointestinal tract that activates GHSR, and the recently described liver-expressed antimicrobial peptide 2 (LEAP2), mainly expressed in the liver and small intestine that blocks GHSR activation. GHSR also displays some ligand-independent actions. In vitro, GHSR has an unusually high constitutive activity that activates intracellular signaling with ~ 50% of its maximum activity, in the absence of ghrelin. LEAP2 reduces the constitutive activity of GHSR, indicating that this ligand also acts as an inverse agonist of the receptor. In addition to its intrinsic constitutive activity, GHSR can allosterically interact with other G-protein-coupled receptors and induce mutual changes in their activities. Therefore, different molecular mechanisms can modulate GHSR activity and, as a consequence, its physiological impact.
The questions we are trying to answer are related to: