Endocrine Abstracts

Mutations in the melanocortin-4 receptor (MC4R) are the most common cause of monogenic obesity. The majority of MC4R mutations are predicted to cause the receptor to aberrantly fold. Misfolded MC4R fails to traffic to the plasma membrane (PM) and is retained in the endoplasmic reticulum (ER). Recent studies with other G-protein coupled receptors have shown that stabilisation of misfolded receptor, by pharmacological chaperones, promotes trafficking to the cell surface where th...

Familial Glucocorticoid Deficiency type 2 (patients with normal MC2R) is associated with mutations in the MRAP (Melanocortin Receptor Accessory Protein) gene. In order to investigate the function of this novel single transmembrane domain protein, CHO and SKN-SH cells were transfected with MRAP-FLAG and/or MC2R-GFP constructs and imaged using confocal microscopy. Although the MC2R-GFP failed to be expressed at the cell surface when transfected alone, it was found to be expresse...

Familial Glucocorticoid Deficiency (FGD) [OMIM #202200] is an autosomal recessive disorder resulting from resistance to the action of adrenocorticotropin (ACTH) on the adrenal cortex to stimulate glucocorticoid production. It has previously been linked to mutations in the ACTH receptor (ACTHR) [FGD type 1] and a locus on chromosome 8q, but 70% of cases have no known cause. The aim of this study was to identify additional loci and genes for FGD using a linkage mapping strategy....

Pituitary adenomas are present in ∼25% of autopsy samples, and recent studies have also suggested that clinically important pituitary adenomas are some 5 times more common than previously recognised. Acromegaly is almost always due to a sporadic growth-hormone secreting pituitary adenoma, but familial acromegaly has been reported occasionally. Linkage and loss of heterozygosity studies have shown that it is caused by a tumour suppressor gene located at 11q13; very recent...