Endocrine Abstracts

The lack of proper career structure for non-clinical researchers has become an endemic problem for the thousands of biomedical science post-graduates and post-doctoral researchers in the UK. Traditionally, undertaking a stint at a recognised research institute in the USA was seen as a major way of guaranteeing success in obtaining academic appointments at UK universities. However, have the costs, inconveniences and competition for suitable funding made this avenue for career p...

The family of calcium/calmodulin-dependent protein kinases (CaMK) are major effectors of calcium binding proteins in virtually all systems. Recently, CaMKs have been implicated in regulating pituitary and hypothalamic gene transcription to control the expression of gonadotrophin hormones and adrenocorticotrophin in the pituitary, and as a pivotal protein in the satiety pathway. Despite these observations, the spatial and temporal expression of the CaMKs is poorly documented an...

Human skin is a target tissue for circulating androgens released from the adrenal glands and gonads but local steroid production may also occur in human skin. StAR is a cholesterol transporter protein that controls the rate-limiting step in steroid synthesis and is regulated by steroidogenic factor (SF-1) in the adrenal glands. We have demonstrated the expression of StAR mRNA by RT-PCR in primary dermal papilla cells and in the immortalised human keratinocyte cell line HaCaT. ...

Several recent studies have identified Npr2 gene mutations (encoding the guanylyl cyclase B (GC-B) receptor) as causing dwarfism and achondroplasia. Npr2 null mice have a similar bone phenotype, pituitary growth hormone deficiency and female infertility. As the endogenous ligand for GC-B, C-type natriuretic peptide (CNP) is expressed at high levels in the anterior pituitary of rats and mice, we examined whether components of the natriuretic peptide system were al...

Current therapeutics target cGMP in treating erectile dysfunction and other cardiovascular disorders. In the endocrine system, cGMP mediates the vast majority of biological effects of the natriuretic peptides (ANP, BNP and CNP) acting via their specific guanylyl cyclases receptors (GC-A and GC-B). There are severe endocrine consequences for mice and humans exhibiting mutations to GC-B receptors, including achondroplasia, growth hormone deficiency and female infertility. Despit...

The nuclear receptors, NR5A1 (SF-1), NR5A2 (LRH-1) and NR0B1 (DAX-1), are key regulators of gene expression and development in endocrine tissues. NR5A1 regulates endocrine development and function, and is an important regulator of gene expression in pituitary gonadotrophs. In contrast, little is known regarding the role of NR5A2 in pituitary function. Using a range of anterior pituitary-derived cell lines and primary rat pituitaries, we have investigated the expression and act...

The transcription factor, Steroidogenic factor-1 (SF-1/NR5A1) is the only specific marker of the VMH, to date. Total SF-1 deficiency results in defective VMH neuronal differentiation and architecture, and mice heterozygous for SF-1 (SF-1+/−), or conditionally depleted of SF-1 in the VMH show reduced levels of the neurotrophin Bdnf and an increased propensity for weight gain. Recent studies have suggested several putative SF-1 target genes in the VMH tha...

The orphan nuclear receptor, steroidogenic factor-1 (SF-1) regulates gonadotroph development and gene expression. In the absence of an identified ligand, SF-1 has been shown to be constitutively active and recent studies reveal that post-translational modification may regulate its transcriptional activity. The Ser 203 residue, proximally located to helix 1 of the ligand binding domain (LBD) of SF-1, resides in a consensus MAPK phosphorylation site, and is required for full tra...

The cellular and molecular mechanisms underlying the actions of BMP-2 to induce gonadotroph-specific gene expression during pituitary development are poorly understood. We have characterised BMP receptor (BMP-R) expression in two gonadotroph models, the alphaT3-1 and LbetaT2 cells, which represent different stages of gonadotroph development. Signal transduction via BMP-R requires a heterodimeric complex between type I (A or B) and type II receptors. RT-PCR for BMP-R, using sub...

Introduction: Mutations in AIP have been associated with the familial isolated pituitary adenoma (FIPA) syndrome, an autosomal dominant disease with incomplete penetrance characterised by pituitary adenomas in a familial setting. However, the mechanisms by which AIP inactivation promotes pituitary tumorigenesis are unknown. Studies of AIP in model organisms, such as the fruitfly, harbouring the AIP orthologue CG1847, as well as the zebrafish, are theoretically promising models...