Endocrine Abstracts

Gene delivery to the CNS is undermined by the lack of suitable vectors capable of delivering genes with sufficient specificity, efficacy and safety. In previous studies we have shown that bacteriophage particles, which lack tropism for mammalian cells, can be genetically modified to display specific ligands that allow binding, internalisation and cell transduction of receptor-bearing target cells. Moreover, phage particles can be forced to evolve using combinatorial techniques...

The insulin-like growth factor binding proteins (IGFBPs-1 to -6) complex IGF-I and -II and were originally assumed to limit IGF access to the main IGF signalling receptor (IGFR) and decrease IGF activity. IGFBP-5 is the most conserved of the IGFBPs. Examination of its primary sequence reveals that, in addition to the key IGF binding domain, additional functional motifs are present that are not related to its IGF binding function.IGFBP-5 is upregulated du...

It is now well known that peripheral nervous system (PNS) is able to synthesize neurosteroids and to convert them, or hormonal steroids coming from the periphery, in neuroactive steroids. Moreover, PNS possess both classical (e.g., progesterone receptor, PR, androgen receptor, AR) and non-classical (e.g., GABAA receptor) steroid receptors and consequently may represent a target for the action of neuroactive steroids. Our data have indicated that neuroactive steroids, like for ...

GnRH is essential on reproductive physiology and behaviour. Early in development, GnRH-1 neurons undergo a migratory process from the olfactory placode (OP) to the hypothalamus. Failure of GnRH-1 migration and abnormal olfactory bulb (OB) characterize Kallmann's syndrome (KS) resulting in hypogonadotrophic hypogonadism and anosmia. The X-linked form of KS is due to a dysfunctional KAL-1 gene, which encodes anosmin-1. An autosomal dominant form of KS results from disrupted K...

While the hypothalamo-pituitary axis is known to contain high levels of basic FGF (FGF2) and its high affinity receptor FGFR1, the physiological role of FGF2 in this region needs elucidation. Here, we demonstrate that FGF2 and arginine vasopressin (AVP) co-localize within the cytoplasm of nearly all supraoptic and paraventricular magnocellular neurons of human hypothalamus as well as the axonal processes of the neurohypophysis. High-resolution confocal imaging indicates that F...

(This poster is based on OC11)...

The IGF-I receptor (IGF-IR) growth/survival pathways are engaged in crosstalk with pathways induced by cell-cell interactions. Different elements of the IGF-IR signalling system also affect the phosphorylation status of molecules involved in the regulation of cadherin-mediated cell-cell adhesion, such as catenins. In addition, the IGF-IR has been shown to co-precipitate with cell adhesion complexes.In this study, the crosstalk between IGF signalling and ...

Igfbp5 is the most conserved of the six members of the Igfbp family, which orchestrate the actions of the insulin-like growth factors (IGFs) systemically via blood and locally within tissues. Igfbp5 is upregulated in key lineages during development (e.g. muscle) and pathologies (e.g. rhabdomyosarcoma).To highlight the range and extent of Igfbp5 actions in vivo, we generated novel lines of transgenic mice t...

The resin of the guggul tree (Commiphora mukul) has been used for millennia in Ayurvedic medicine to treat a variety of ailments. Extracts of this resin have been reported to lower LDL cholesterol in humans, and the plant sterol guggulsterone (4,17(20)-pregnadiene-3,16-dione) is thought to be the active agent. We have found that guggulsterone is an antagonist ligand for the nuclear the bile acid receptor, FXR. Guggulsterone treatment lowers hepatic cholesterol levels in wild t...

A small subset of genes in the human genome encode peptides that have intrinsic therapeutic value. These genes, collectively known as the "theratome", most often encode ligands and are of particular interest to endocrinology. The genes encoding growth hormone, somatostatin, erythropoeitin, neuropeptides, placental and pituitary hormones are all examples of the theratome. Unfortunately, the sequences encoding many ligands are not always detectable within the sequences of their ...