Endocrine Abstracts

A male patient treated with a thiazolidenedione (TZD) PPAR gamma agonist for Type 2 diabetes had a dramatic worsening of his thyroid eye disease (TED), which had been stable and inactive for more then two years. Expansion of the orbital fat seemed to be the underlying cause and we have investigated the effects of a PPAR gamma agonist (and subsequently an antagonist) on the adipogenesis of preadipocytes from 10 different patients, representing several fat depots, including TED ...

The critical role of thyroid hormones (TH) in normal human growth and fetal development is well recognised. The availability of tri-iodothyronine (T3) to bind to thyroid hormone receptors is determined by the local concentrations of T3, as well as the local action of deiodinase enzymes that determine conversion of T4.Quantitative real time RT-PCR was used to quantify the expression of mRNAs encoding the specific deiodinase subtypes (D1, D2 & D3) in h...

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...

The risk of bone fracture at most skeletal sites rises rapidly with age. Changes in bone mass account for only a small part of this increased risk - an additional factor is the progressive reduction in the ability to form new bone. This decrease in bone formation and increased fracture risk is reminiscent of changes seen with glucocorticoid excess, however, circulating corticosteroid levels do not change with age. We have proposed that local rather than circulating levels of c...

Synthetic C19 gestogens which are used in combination with testosterone as hormonal contraception in men bind to both the androgen and progesterone receptor. The relative contribution of these two components is unclear. In this study, we have compared the effect of a synthetic gestogen (desogestrel) with naturally occurring progesterone on the pattern of secretion of LH and FSH in healthy volunteers. Twenty men aged 18-40 were randomised to receive either progesterone (gestone...

The most robust biochemical marker for the diagnosis of PCOS is hyperandrogenism (androstenedione, testosterone), thought to originate from the ovaries and/or adrenals. However the change in circulating androgen/LH ratios with increasing body mass in women with PCOS suggests the autocrine generation of androgens within adipose tissue itself. The enzyme 17beta hydroxysteroid dehydrogenase (17betaHSD) which has seven human isoforms is an important regulator of sex steroid metabo...

DHEA, the most abundant circulating adrenal steroid in humans has an uncertain role. DHEA declines with age, and has been suggested to antagonise some glucocorticoid actions. Previous studies have suggested that DHEA may have immunoregulatory, and metabolic functions. In rodent studies DHEA has been shown to improve insulin sensitivity, possibly by opposing glucocorticoid action. Glucocorticoids act on multiple tissues and employ a variety of mechanisms of action.<p class...

The glucocorticoid receptor antagonist, RU486, binds to the glucocorticoid receptor (GR) with high affinity, and allows both nuclear localisation and also DNA binding. However, the DNA bound GR does not activate target gene transcription. This suggests that the ligand-binding domain of the GR is required to interpret agonist and antagonist ligands, and transmit those signals to the basal transcriptional machinery. Adaptor proteins play an important role in transducing the effe...