Endocrine Abstracts

An intact pituitary-adrenal axis is essential for life, yet is entirely dependent on a system with no inbuilt redundancy. Central to its activity a single peptide hormone, ACTH, acts on a single G protein-coupled receptor (GPCR) at the adrenal cortex. This ACTH receptor, otherwise known as the Melanocortin 2 receptor (MC2R) is the smallest of all GPCRs, consequently being highly hydrophobic and lacking a signal sequence – hence its resemblance to a “blob”. Multi...

After the crisis of diagnosis and surgery for craniopharyngioma, patients and families are immediately faced with the lifetime challenge of pituitary replacement therapy. The endocrine nurse assists the patient in adapting to the regimen required for a return to normal hormonal balance and optimal health. Nurses teach the purpose of prescribed hormones, and reinforce the most effective method and scheduling of each medication; this must be individualized for each patient. Defi...

It is a widely held view that genetic mutations cause diseases by interfering with the normal function of the protein encoded by the gene in question, and there are many examples of this phenomenon. However it is increasingly apparent that in some cases mutant proteins have altered function because they have failed to assemble correctly, or because they fail to reach the correct compartment of the cell correctly. Recent work investigating certain inherited disorders of the adr...

Adrian Clark, Barts & the London, QMUL, London, United Kingdom. AbstractAdrian Clark graduated in Medicine from St Bartholomew’s Hospital Medical College in 1976. After several junior medical training posts at Barts, Nottingham, Hammersmith and Guys, he spent two years at the NCI in Bethesda working on the cloning of the EGF receptor with Ira Pastan, then later moved to work for three years with Kevin Catt, al...

Clinical Case: A 51 year old woman of south Asian descent was referred by her GP to outpatient endocrine clinic for assistance with her mixed hyperlipidaemia (Cholesterol 9.5 mmol/L, HDL Cholesterol 1.03 mmol/L Triglycerides 6.7 mmol/L). Her past medical history included a previous hemithyroidectomy for removal of a thyroid nodule (histologically benign) and obesity.The patient’s symptoms were of weight gain (5 kg in 18 months...

Clinical Case: A 51 year old woman of south Asian descent was referred by her GP to outpatient endocrine clinic for assistance with her mixed hyperlipidaemia (Cholesterol 9.5 mmol/L, HDL Cholesterol 1.03 mmol/L Triglycerides 6.7 mmol/L). Her past medical history included a previous hemithyroidectomy for removal of a thyroid nodule (histologically benign) and obesity.The patient’s symptoms were of weight gain (5 kg in 18 months...

The melanocortin 2 receptor accessory protein (MRAP) is essential for the functional expression of the ACTH receptor/melanocortin 2 receptor (MC2R). The pituitary hormone ACTH acts via this complex to stimulate glucocorticoid production in the adrenal cortex. Using the bioluminescence resonance energy transfer (BRET) system we investigated the formation of MC2R–MRAP homo/heterodimers in living cells and the influence of ACTH on these interactions. ACTH was found to have a...

ACTH insensitivity or Familial Glucocorticoid Deficiency (FGD) is an autosomal recessive disorder that presents in early childhood usually with hypoglycaemia and seizures, infection or malaise and skin pigmentation. Plasma cortisol is low or undetectable and ACTH markedly elevated. Renin and aldosterone are not markedly disturbed. FGD results from mutations of the ACTH receptor in about 25% of cases. We have sought further genetic causes of this disorder using a homozygosity m...

Adrenocorticotrophic hormone (ACTH), a 39 amino acid peptide is the principal regulator of adrenal steroidogenesis and is thus essential for life. ACTH mediates its effects through a cell surface G-protein coupled receptor which elevates the intracellular production of cAMP through adenylate cyclase. There have been significant difficulties in developing a suitable heterologous expression system to study the ACTH receptor (or melanocortin 2 receptor - MC2R), and we have postul...

The mechanisms which control the cell cycle and growth of adrenocortical cells remain largely uncharacterized. ACTH binds to its G protein-coupled receptor (GPCR), the melanocortin 2 receptor (MC2R) in the adrenal cortex and mediates the production of cAMP resulting in steroidogenesis. ACTH however also remains a candidate for the control of growth in the adrenal cortex. It is well known to have a growth promoting effect in vivo but has an opposing effect in some cell systems ...