Endocrine Abstracts

The development of the growth hormone antagonist, Pegvisomant, is a story of modern drug design. The original observation was by John Kopchick, who noted that transgenic mice with a mutation in the third alpha helix of the GH molecule had a dwarf phenotype. This is the basis for the site 2 mutation (G120K) in the GH molecule that blocks GH signaling. At the same time the Genetech group of James Wells had characterised the crystal structure of the GH/receptor complex demonstrat...

Background: Leptin is an important regulator of the immune response. Therapeutics that modulate leptin signalling are considered to be a potential targets in a number of immune related conditions. The role of leptin antagonists to suppress the immune system, slowing the progression of autoimmune diseases is a widely discussed idea. However, leptin agonists may also be useful to up-regulate the immune response during malnutrition. The aim of this project was to develop long-las...

Introduction: Identifying leptin agonists and antagonists requires a reliable bioassay responsive to physiological levels of leptin. The leptin receptor exists in multiple isoforms but Ob-Rb, the full length receptor, mediates the biological actions of leptin and its predominant signalling pathway is through STAT3. We report the development of a bioassay based on a STAT3 firefly luciferase reporter. Materials and Methods: HEK 293 cells were transfected with varying amounts of ...