Endocrine Abstracts

Cytochrome P450arom (aromatase), a marker of granulosa cell differentiation, and CTGF mRNA expression are inversely related in the developing rat follicle, but the cause/effect nature of the relationship is not known. Here, we used semi-quantitative in situ hybridization to analyze the expression of these genes during follicular development in the rat. The effect of CTGF on aromatase enzyme activity in isolated granulosa cells was determined by conversion of ...

The Chernobyl accident in 1986 resulted in a release of radioiodine that contaminated large areas of what are now Belarus, Northern Ukraine and a neighbouring area of Russia. The major health consequence of the accident to date has been a large increase in thyroid cancer in those who were children or adolescents at the time of exposure. The increase is mostly restricted to an increase in papillary carcinoma, of a particular subtype (the solid follicular variant) and associated...

Adverse events in utero permanently alter the structure and physiology of adult offspring, a phenomenon termed 'foetal programming'. In particular, low birth-weight is associated with an increased risk of adulthood hypertension. Glucocorticoid (GC) administration during pregnancy reduces offspring birth-weight and GCs directly elevate blood pressure (BP) in both humans and rodents. Circulating and local renin-angiotensin-aldosterone (RAAS) system(s) may be involved in programm...

In humans only thyroid hormone (T3) receptor (TR) beta1 and beta2 mRNAs have been identified, whereas alternative splicing generates recently characterised beta3 and deltabeta3 transcripts in rat and further N-terminal isoforms in other species. We investigated whether additional transcripts arise from the human TRbeta gene by 5'-RACE. Five distinct TRbeta1 transcripts were isolated, including the previously described TRbeta1 mRNA and four novel 5'-untranslated region (5'-UTR)...

The calcium sensing receptor (CaSR) plays a central role in altering the secretion of parathyroid hormone (PTH) in response to alterations in extracellular calcium, and four studies have reported an association between CaSR polymorphisms and serum Ca 2+, serum PTH, and bone mineral density (BMD). However, two other studies have failed to detect such associations. We have therefore undertaken studies to investigate the Ala986Ser, Arg990Gly, and Gln1011Glu CaSR polymo...

Proadrenomedullin N-terminal 20 peptide (PAMP) and adrenomedullin are hypotensive peptides that are cleaved from the proadrenomedullin peptide. Adrenomedullin can act via the complex calcitonin receptor like receptor (CRLR) and receptor activity modifying protein (RAMP) 2 or the putative receptor, CRLR/RAMP3 complex. CGRP (Calcitonin gene related peptide) binding is conferred by the CRLR/RAMP1 complex. This study was carried out to see how adrenomedullin and PAMP affected the ...

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...

The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D3), is synthesised by the enzyme 25-hydroxyvitamin D3-1alpha-hydroxylase (1alpha-hydroxylase). The principal site of 1alpha-hydroxylase activity is in the proximal tubule of the kidney. In order to investigate renal vitamin D metabolism we have used a human proximal tubule cell line, HKC-8. We have previously shown that synthesis of 1,25D3 activity in these cells is sensitive to the concentration of calcium and North...

PTTG has a dual role in tumorigenesis. Firstly, it regulates expression of basic fibroblast growth factor (FGF-2), and secondly, as a human securin homologue, it inhibits sister chromatid separation in mitosis. Securins must be degraded at Destruction Box (DB) motifs by an anaphase promoting complex (APC), before cell division can proceed. We have used a variety of approaches to examine the precise roles of the PTTG Destruction Box and FGF-2 stimulation in cell transformation....

Sodium transport across the human ocular non-pigmented ciliary epithelium (NPE) is fundamental to the production aqueous humour and maintenance of intraocular pressure. In sodium transporting tissues, serum and glucocorticoid regulated kinase isoform 1 (SGK1) has been identified as an early corticosteroid target gene in the activation of pre-existing epithelial sodium channels (ENaC). We previously demonstrated the presence of both the mineralocorticoid (MR) and glucocorticoid...