Endocrine Abstracts

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 ...

IGFBP-5 is the most conserved of a family of high affinity proteins that modulate IGF activity. It is upregulated in key lineages during their differentiation and development. In addition to domains associated with IGF binding, IGFBP-5 also possesses motifs that may be involved with its recently demonstrated IGF-independent actions. We have therefore examined the hypothesis that IGFBP-5 is important during development. We have generated mice overexpressing IGFBP-5 using an ear...

Although thyroid hormone (T3) and the T3-receptor (TR) alpha gene are essential for skeletal development, T3-signalling pathways in bone have not been characterised. We identified fibroblast growth factor receptor-1 (FGFR1) as a novel T3-inducible gene in osteoblasts by subtraction hybridisation. FGFR1 mRNA was induced 2-3 fold in osteosarcoma cells and primary cultured osteoblasts treated with T3 (0.1-1000nM, 0-48h) and FGFR1 protein was stimulated 2-4 fold over the same peri...

Thyroid hormone (T3) receptor beta (TRbeta) mutations cause resistance to thyroid hormones (RTH), characterised by decreased tissue sensitivity to T3. The TRbetaPV mutation (C-insertion at codon 448 leads to a frameshift of the carboxy-terminal 14 amino acids) was derived from a patient with severe RTH and generates a receptor lacking T3-binding and transactivation activities. Heterozygous mutant mice have a mildly impaired pituitary-thyroid axis; severe RTH and limb shortenin...

Growth in utero depends on adequate development and function of the fetal / maternal interface. During pregnancy, the insulin-like growth factors (IGFs), which are known to be critically involved in placental development, are controlled by a binding protein - IGFBP-1 - produced by maternal decidualised endometrium. We have recently found that decidua also produces a protease which cleaves IGFBP-1 into fragments that are unable to bind ligand. This study aimed to identif...

Tyrosine kinase inhibitors have previously been shown to inhibit DNA synthesis in human pituitary adenomas (Jones et al JCEM 1997; 82: 2143-7). ZD1839 ('Iressa'), a selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, is currently undergoing clinical trials in human cancers. We have investigated the effects of ZD1839 and EGF in the human pituitary cell line HP75 (derived by SV40 transfection of a human pituitary silent gonadotrophinoma) and in s...

CTGF is a heparin-binding multi-domain growth factor, stimulated by TGF- beta, and implicated as a paracrine regulator of mitosis, angiogenesis, cellular taxis and remodelling of the extracellular matrix in diverse epithelial cell layers. To examine the roles of CTGF in the ovarian paracrine system, we studied rat granulosa cell CTGF gene expression both in vitro and in vivo. Untreated granulosa cell monolayers from DES-treated immature rats expressed abundant ap...

An increased number of medium-sized antral follicles is one of the characteristic features of polycystic ovaries (PCO) but little is known of the preantral stages of follicle development. The aim of this work was to explore small preantral follicle development in ovulatory and anovulatory PCO and to compare it with that in normal ovaries. Small ovarian cortical biopsies were obtained with informed consent and local ethics committee approval from 27 women with PCO, 13 anovulato...