Endocrine Abstracts

Background: Familial Glucocorticoid Deficiency is an autosomal recessive disorder characterised by ACTH resistance of the adrenal cortex, leading to isolated glucocorticoid deficiency. Causative genes include MC2R, its accessory protein MRAP and StAR which account for 50% of cases. Recently nicotinamide nucleotide transhydrogenase (NNT) has been associated with a further 10% of cases. NNT generates the high concentrations of NADPH in mitochondria necessary for detoxification o...

Animal models are valuable tools in fertility research. Worldwide, there are more than 1000 transgenic or knockout mouse models available showing a reproductive phenotype; almost all of them exhibit an infertile or at least subfertile phenotype. By contrast, animal models revealing an improved fertility phenotype are barely described. We developed two outbred mouse models exhibiting a ‘high-fertility’ phenotype. These mouse lines were generated via selection over a t...

Expression of the ACTH receptor (MC2R), a 7 transmembrane GPCR, has been difficult to achieve in cell lines that are not of adrenal origin. Heterologous expression of this gene in many cell lines (CHO, Hela, H295R, HEK293) produces a protein that is trapped in the ER, suggesting that an accessory factor(s) might be necessary to traffic MC2R through the cell. We recently identified such an accessory factor, MRAP that rescues MC2R expression in some, but not all, cell lines. Mut...

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....