Endocrine Abstracts

Can we drug receptors for microbially-produced metabolic hormones and for what indications? G protein-coupled receptors (GPCRs) have been a major group of druggable cell surface receptors and therapeutics targeting many hormone-activated GPCRs have been developed. A number of products of the processing and metabolism of foodstuffs act in a hormone-like manner and these include both short and medium chain length free fatty acids. Short chain fatty acids produced in large amount...

The pathogenesis of gonadotrophin secreting pituitary tumours (gonadotrophinomas) remains poorly understood. BMP2, known to be important in the control of cell proliferation and differentiation, is essential for commitment of undifferentiated pituitary cells to the gonadotroph cell lineage. Attenuation of its expression is critical in allowing terminal differentiation. BMPs are associated with up-regulated expression of Id (Inhibitors of differentiation) proteins with predicte...

The pharmacology and function of G protein-coupled receptors (GPCRs) is frequently studied following expression of a single receptor in heterologous cell lines. However, many GPCRs are co-expressed. We wished to investigate how expression of pairs of receptors might modulate their function. Using a Human Embryonic Kidney 293 cell line in which the CB1 cannabinoid receptor was expressed constitutively and in which varying levels of expression of the orexin-1 receptor could be i...

Bone morphogenetic protein-2 (BMP-2) signal transduction requires heterocomplexing between type II receptors and different type I (α or β) receptors resulting in the activation of different signalling pathways. Previously, we have used αT3-1 and Lβt-2 cell lines, which are representative of different stages of gonadotroph development, to demonstrate differential expression of the receptor isoforms during gonadotroph maturation. BMPR-Iα and II mRNA and ...

The pathogenesis of gonadotrophin secreting pituitary tumours (gonadotrophinomas) remains poorly understood. Bone morphogenetic proteins (BMPs) are important for the control of cell proliferation and differentiation and BMP2 is essential for commitment of undifferentiated pituitary cells to the gonadotroph cell lineage. In addition, BMPs have been implicated in tumourigenesis in a variety of tissues, associated with up-regulated expression of Id (Inhibitors of differentiation)...

Bone morphogenetic proteins (BMPs) regulate growth, differentiation and apoptosis in a variety of tissues and have crucial roles in the regulation of reproduction. BMPs bind specific Type II receptors and form complexes with Type I receptors (Alk2, 3 or 6) whereby the Type II receptors activate Type I receptors by phosphorylation. BMP2 and 4 play a crucial role in the development of the gonadotroph cell lineage during mouse pituitary morphogenesis and BMP6, 7, and 15 stimulate...

SHOX has been implicated in the regulation of bone growth and modelling. Haploinsufficiency and heterozygous mutations of SHOX are associated with Lerri Weil Dyschondrosteosis (LWD). The cardinal features of LWD are mesomelic limb shortening and Madelung deformity. Histological studies demonstrate premature fusion of the ulna border of the radial epiphysis and disordered osteoblast maturation and orientation. In view of these observations we investigated the role of SHOX in th...

T3 and T4 rapidly activate intracellular signalling cascades via thyroid hormone receptor (TR)-independent actions, suggesting the existence of a plasma membrane receptor. Recent studies support a role for the RGD recognition site of integrin, a transmembrane glycoprotein, as a cell surface TR. We have demonstrated, using PCR and Western blotting, the expression of integrin αVβ3 mRNA and protein in the transformed human osteosarcoma cell line MG...

Nuclear receptors regulate biological responses by acting as ligand dependent transcription factors in target cells. Their ability to modulate transcription is mediated by cofactors which are recruited to target genes by binding to receptors. They can either act as coactivators or corepressors and their roles include their ability to remodel chromatin and to recruit the basic transcription machinery. NRIP1 is transcriptional repressor which is recruited to nuclear receptors in...

Reorganization of the actin cytoskeleton could coincide with the activation of several seven transmembrane receptors (7TM receptors) (1). Stimulation of Rho family members leads to rapid remodeling of the actin cytoskeleton and subsequent stress fiber formation and certain 7TM receptors were shown to induce Rho-dependent responses via heterotrimeric G-proteins. Gα12, Gα13 as well as Gαq/11 can link 7TM receptors to RhoA activatio...