Endocrine Abstracts

Fellowships are grants made available to researchers to support both the costs of the research and the salary of the applicant. Fellowship schemes are available from the Research Councils, the Wellcome Trust, the Royal Society and several other charities. Although awards are available to researchers with established positions to allow them to be relieved of their teaching/admin duties, most awards are designed to promote the careers of postdoctoral scientists. The awards are m...

With the cloning of the gene encoding pro-opiomelanocortin (POMC) it became apparent that several other peptides distinct from ACTH would be co-secreted from the anterior pituitary into the circulation. This begged the question as to whether these peptides have any biological actions on the adrenal, or to that matter any other tissue. Over the past two decades it has become apparent that the N-terminal fragment known as pro-gamma-MSH plays a role in adrenal physiology.<p c...

The N-terminal fragment of human POMC consists of a 76 residue peptide (also known as pro-gamma-MSH) that contains the sequence of gamma-MSH in its C-terminus. Previous studies have demonstrated that the N-terminal portion not containing the gamma-MSH sequence is a potent adrenal mitogen while gamma-MSH itself can act synergistically with ACTH to increase steroid output.Since previous studies [1] have suggested that N-POMC 1-28 can stimulate the ERK path...

The pro-opiomelanocortin (POMC)-derived peptides, pro-gamma-MSH and Lys-gamma3-MSH, have been shown to potentiate the steroidogenic action of Adrenocorticotropic hormone (ACTH) on the adrenal cortex. The molecular mechanisms for this potentiation are unclear, but it has been shown that gamma-MSH peptides promote mitochondrial cholesterol accumulation in the adrenal cortex by upregulating the activity of Hormone Sensitive Lipase (HSL) (1). HSL activity is regulated either by up...

Lys-gamma3-MSH is a peptide derived from the multihormone precursor protein pro-opiomelanocortin (POMC). Lys-gamma3-MSH increases cholesterol ester hydrolysis and mitochondrial cholesterol accumulation in the adrenal gland by activating the enzyme cholesterol ester hydrolase (CEH). Although the receptor through which the actions of Lys-gamma3-MSH on the adrenal gland are mediated remains to be identified, ligand binding studies suggest the existence of binding sites in adipose...

In respect to growth, the adrenal is a dynamic organ that requires constant stimulation from peptides derived from the ACTH precursor pro-opiomelanocortin (POMC) to maintain its tonic state. Previous studies have suggested that the adrenal mitogen resides in the N-terminus of pro-gamma-MSH, which upon cleavage results in the generation of shorter mitogenic peptides not containing the gamma-MSH sequence. This hypothesis has recently been substantiated by our characterisation of...

Background: Numerous studies have reported the role of the N-terminal of pro-opiomelanocortin (N-POMC1-76) and its smaller fragments; 1-28 and 1-49, in adrenal steroidogenesis and mitogenesis. A full understanding of this area will help to understand the pathophysiology of certain adrenal tumours but exactly how these peptides elicit this effect is unclear. We have recently identified an orphan G protein-coupled receptor (GPCR) as a possible N-POMC receptor. Preliminary data s...

Lys-γ3-MSH is a melanocortin peptide derived from the C-terminal of the 16 kDa fragment of pro-opiomelanocortin (POMC). The physiological role of Lys-γ3-MSH is unclear, although it can potentiate the steroidogenic response of adrenal cortical cells to adrenocorticotrophin (ACTH). This effect appears to correlate with an ability to increase the activity of hormone sensitive lipase (HSL) and therefore the rate of cholesterol ester hydrolysis. Ligand binding studies hav...

During the search for the serine protease that cleaves pro-gamma-melatropin to stimulate adrenal growth (Bicknell et al, Cell, 2001, 105: 903), we identified another novel protease which we called AmP. In situ hybridisation detected AmP transcripts in steroidogenic tissues such as the brain particularly in the PVN and the dentate gyrus, in leydig cells of the testis, in underdeveloped follicles in the ovary as well as in the adrenal cortex. Full length cloning identified two s...

We have recently reported that a novel protease found on the surface of cells in the zona glomerulosa of the adrenal cortex specifically cleaves pro-gamma-melanotropin (pro-gamma-MSH) generating the adrenal mitogen, pro-opiomelanocortin, POMC(1-52). RT-PCR of mRNA isolated separately from the pars intermedia and pars distalis suggested that this protease is also expressed in both parts of the pituitary gland but surprisingly confocal microscopy in situ hybridisation located it...