Endocrine Abstracts

Expression of the ACTH receptor, MC2-R, is highly restricted, being detectable in the mouse only in the adrenal cortex and adipose tissue. The promoter of the murine MC2-R contains binding sites for SF-1, a transcription factor that has been shown to be essential for the transcriptional activity of a number of steroidogenic genes. However, SF-1 is not expressed in adipocytes and therefore is not essential for MC2-R expression in these cells. We have investigated the requiremen...

The physiological effects of the pituitary hormone, adrenocorticotropic hormone (ACTH) on the adrenal are mediated by the melanocortin 2 receptor (MC2R), a G protein coupled receptor (GPCR) that signals via adenylate cyclase to elevate intracellular cyclic AMP (cAMP) levels. Therefore the expression and function of the receptor are likely to be the major determinants of the response to ACTH. Following repeated stimulation, the cAMP signal is diminished or desensitised. Desensi...

Background: The ACTH receptor (melanocortin 2 receptor – MC2R) is unique in that it is highly selective for ACTH and excludes all other MSH peptides. This contrasts with all other members of the melanocortin receptor family, which show broader specificity. The specificity of recognition of ACTH by the MC2R appears to depend on the presence of four basic residues, lysine, lysine, arginine, arginine at positions 15–18. Of α-, β- and γ-MSH are either iden...

The murine ACTH receptor MC2-R is primarily expressed in the adrenal cortex and adipocytes where it binds ACTH leading to steroidogenesis and lipolysis, respectively. We have recently shown that the previously described 'adrenal' MC2-R promoter is transiently activated by PPAR gamma 2 early during differentiation of murine 3T3-L1 pre-adipocytes, declining to background levels from a peak of activity seen at day 4 following commencement of adipogenesis. This is mirrored by the ...

The peptide hormone ACTH can stimulate lipolysis and suppress leptin expression in murine adipocytes. These effects are mediated via the Melanocortin 2 Receptor (MC2-R), which is expressed when 3T3-L1 cells are induced to differentiate into adipocytes. In this study we have investigated the transcriptional activation of the MC2-R gene during adipogenesis.5' deletion analysis of the murine MC2-R promoter revealed the presence of a transcriptional enhancer...

The Melanocortin 2 Receptor (MC2R) is best known for its role in the adrenal cortex where it couples the action of ACTH to steroidogenesis, however it is also expressed by the adipocyte. We set out to characterize the up-regulation of the MC2R in the 3T3-L1 fibroblast, which can be induced to undergo adipogenesis.RT-PCR using primers specific to exons 1 and 2 amplified three bands in differentiated 3T3-L1 adipocytes which sequencing revealed to be distin...

The molecular mechanisms underlying adrenal adenomas have not yet been elucidated. Many groups have sought mutations within the ACTH receptor as well as its downstream signalling pathway, although none have yet been identified. However, mutations in the alpha regulatory subunit of the cAMP dependant Protein Kinase A (PRKAR1A) have recently been described in more than 50% of patients with Carney complex. This syndrome is characterised by nodular adrenocortical hyperplasia as we...

The molecular mechanisms underlying adrenal adenomas have not yet been elucidated. Many groups have sought mutations within the ACTH receptor as well as its downstream signalling pathway, although none have yet been identified. However, mutations in the alpha regulatory subunit of the cAMP dependant Protein Kinase A (PRKAR1A) have recently been described in more than 50% of patients with Carney complex. This syndrome is characterised by nodular adrenocortical hyperplasia as we...

A 24 year old man was admitted by the Surgeons with left sided abdominal pain. He was febrile and tachycardic and found to have raised inflammatory markers. Abdominal CT scan revealed a 6 cm left adrenal haemorrhage with no evidence of an underlying lesion. Initial endocrine investigations were unremarkable for Cushings, Conn’s and adrenal insufficiency. Norepinephrine levels were high but settled subsequently. He had a coagulopathy and evidence of reactivation of EB viru...

Investigation of parathyroids in mouse models is hampered by difficulties in identifying the small glands. We developed a microsurgical technique to identify murine parathyroids by dissecting from the distal thyrothymic ligament to the lower thyroid pole (LTP). Parathyroids were identified in 100 mice which comprised: 48 mice deleted for a cell-division-cycle 73 gene allele (Cdc73+/−), involved in the hyperparathyroidism-jaw tumour syndrome; ...