Endocrine Abstracts

The metabolic enzyme adenosine monophosphate-activated protein kinase (AMPK) was originally discovered as a regulator of cellular energy homeostasis. It protects and replenishes cellular ATP via stimulating catabolic processes such as glycolysis and lipid oxidation, and inhibiting anabolic processes such as lipid synthesis and gluconeogenesis in peripheral tissues (liver, adipose or muscle cells). However, more recently it has emerged that AMPK activation in the hypothalamus l...

Numerous growth factors, oncogenes, tumour suppressor genes and hormonal influences have been implicated in pituitary tumorigenesis. We have demonstrated that the PI3K-Akt pathway is upregulated in pituitary tumours and since Akt is a major downstream signalling molecule of growth factor-liganded tyrosine kinase receptors it is possible that an abnormality at this level could be the primary driver of pituitary tumorigenesis. The serine/threonine kinase B-Raf functions as a dow...

Ghrelin is a novel growth hormone-releasing peptide, recently identified in the rat stomach as the endogenous ligand for the growth hormone secretagogue-receptor (GHS-R). Previously, regulation of GH release was thought to occur primarily via a phasic interaction between two hypothalamic neuropeptides, GHRH and somatostatin. It is now thought that ghrelin is an important third factor in the regulatory pathway. In addition to its GH-releasing activity ghrelin may have other act...

Context: Normosmic idiopathic hypogonadotropic hypogonadism (nIHH) is a rare endocrine disease in which patients have isolated gonadotropin releasing hormone (GnRH) deficiency in the context of otherwise normal structure and function of anterior pituitary and hypothalamus with normal olfactory ability.Objective: To explore the underlying pathogenic defect in patients with delayed puberty.Patients: We investigated genetic defects in...

Background: Pituitary adenomas are the most common intracranial neoplasm, with a slow-growing, locally invasive phenotype. Some result from syndromes or isolated germ-line mutations, while approximately 60% have no currently identified somatic mutation implicated in tumorigenesis. High throughput technologies such as microarray, RNA sequencing (RNAseq) and next-generation sequencing (NGS, incorporating whole genome- and exome sequencing) have recently been used to identify alt...

Objectives: Somatotropinomas form three subgroups with distinct methylation profiles1, one matching the sparsely granulated (SG) and the other two matching the densely granulated phenotypes (DG-A and DG-B). Publicly accessible raw methylation data1 and our RNA microarray data were analysed to identify differentially methylated regions (DMRs) and enriched genes between SG, DG-A and DG-B and normal anterior pituitary gland (NP), genes showing differential m...

Background: Germline mutations in the aryl-hydrocarbon receptor interacting protein (AIP) gene have been implicated in the tumorigenesis of patients with familial isolated pituitary adenoma (FIPA). Around 25% of FIPA patients have an identified AIP mutation; in the remainder of FIPA patients, molecular mechanisms involved in pituitary tumorigenesis have yet to be elucidated.Aims: To identify the genes and molecular mechanisms involved i...

Background: Olfactory neuroblastoma (ONB), a neuroendocrine nasal tumour, exhibits a range of phenotypes from indolent to very aggressive. Even early disease is associated with high (60%) recurrence rates, while advanced disease has 1.5y disease-free and 2.5y overall mean survival. Medical treatments against primary and recurrent disease as well as prognostic biomarkers are urgently required. The few studies available suggest that mTOR/MAPK and Sonic Hedgehog signalling has a ...

Background: Germline mutations of the AIP tumour suppressor gene are associated with familial and sporadic pituitary adenomas, yet the tumorigenic mechanisms remain unclear. In addition, AIP protein expression in somatotroph adenomas from patients without AIP mutations correlates with clinical behaviour and somatostatin analogues responsiveness. Understanding the regulation of AIP gene expression will help uncover its pituitary tumour-suppressor role.Aim...

Background: Heterozygote mutations in AIP predispose carriers to young-onset pituitary adenomas, most often somatotroph or lactotroph adenomas. No other tumour type has been consistently detected in AIP mutation positive families, despite the fact that AIP is ubiquitously expressed. Current clinical and experimental data suggest that AIP is a tumour suppressor gene.Aims: To investigate the tumour suppressor role of AIP in a non-pituitary malignant cell l...