Endocrine Abstracts

I guess the fact that I was awarded my first MRC grant 30 years ago and my present programme grant runs out at the end of next year gives me at least some personal experience in writing successful grants and thus the reason the Society has asked me to give this talk. In the early 90s I was also a member of the Neuroscience and Mental Health Board of the MRC and so was able to observe the mechanism of grant assessment first hand.I will discuss the various...

Throughout pregnancy, the placenta controls the metabolism of the mother for the benefit of the foetus, sometimes to such an extent that in humans the mother's health is compromised. As there are no neural connections, the main means by which the placenta controls the mother's metabolism must be endocrine in nature. Unfortunately the foetal blood that perfuses the placental/uterine boundary cells to carry oxygen and nutrients back to the foetus will also collect the very hormo...

Phil Lowry, School of Animal and Microbial Sciences, University of Reading, Reading, UK AbstractProfessor Phil Lowry is best known for his research on pituitary hormones, corticotrophin-releasing factor (CRF) and the involvement of neuropeptides in pre-eclampsia. A peptide biochemist by training, his preparations of purified corticotrophin (ACTH) and growth hormone (GH) became standards of the World Health Organisation...

The pregnancy associated plasma proteins (PAPP) -A, -B, -C and -D were first isolated from pregnancy serum in 1974. Since, these proteins have been re-characterised; PAPP-B and PAPP-C are now known as pregnancy-specific beta-1 glycoproteins and PAPP-D as placental lactogen. PAPP-A was subsequently found to be a member of the metzincins family of metalloproteases. Recently we have identified a full-length cDNA encoding the preproprotein of pregnancy associated plasma protein-E ...

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...

Agouti-related protein (AgRP) is a 132 amino acid protein, expressed in the brain where it antagonises the anorexic effect of alpha-MSH through melanocortin 3 and 4 receptors. In situ hybridisation and RT-PCR have shown that AgRP mRNA is also expressed in the steroidogenic zone of the adrenal cortex where levels are up-regulated following 24 hrs of fasting. However, its physiological significance in the adrenal gland is still unknown.To investigate the s...

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...

Adrenal cortical cells are continuously renewed in order to sustain production of relevant zonal steroids. Cell proliferation occurs at the periphery of the cortex where cells subsequently displace centripetally, switching phenotypically as they migrate though the gland and finally undergoing apoptosis at the medullary boundary. However, it is not known which mechanisms cause the cells to differentiate as they cross the zonal boundaries. A candidate group of genes involved in ...