Endocrine Abstracts

Hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and disorders such as congestive heart failure and cirrhosis represents a common problem often encountered in the care of medical patients. Available treatment modalities for disorders of excess arginine vasopressin (AVP) secretion, or action, include fluid restriction, demeclocycline and NaCl administration, but all of these therapies have significant drawbacks and are suboptimal. Over th...

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...

The cell surface calcium receptor is the primary molecular entity regulating secretion of parathyroid hormone (PTH). Activation of this receptor by extracellular calcium inhibits PTH secretion whereas blocking the calcium receptor stimulates secretion of PTH. Chronically elevated levels of PTH, as occurs in hyperparathyroidism, stimulate bone resorption whereas temporary increases in circulating levels of PTH stimulate bone formation. This stimulatory effect on bone has prompt...

The oestrogen receptor (ER) is a ligand-inducible transcription factor that controls expression of a number of genes in a wide variety of tissues. Binding of the natural hormone, oestradiol, triggers dimerisation and nuclear location of the receptor and assembly of a functional transcriptional complex through recruitment of various coactivators.In this talk, I will discuss how knowledge of the structure of the receptor has had a major impact on our under...