Endocrine Abstracts

Expression of the ACTH receptor, MC2-R, is highly restricted, being detectable in the mouse only in the adrenal cortex and adipose tissue. The promoter of the murine MC2-R contains binding sites for SF-1, a transcription factor that has been shown to be essential for the transcriptional activity of a number of steroidogenic genes. However, SF-1 is not expressed in adipocytes and therefore is not essential for MC2-R expression in these cells. We have investigated the requiremen...

Ectopic secretion of adrenocorticotropin (ACTH), from sites such as small cell lung cancer (SCLC), results in severe Cushing's syndrome. ACTH is cleaved from pro-opiomelanocortin (POMC). The syndrome occurs when the highly tissue-specific promoter of POMC is activated. This promoter lies within a defined CpG island. CpG islands are usually considered to be unmethylated in all tissues. We hypothesised that changes in promoter DNA methylation might direct aberrant express...

The global epidemic of obesity has heightened the need to understand the mechanisms that underpin its pathogenesis. Clinical observations in patients with Cushing's syndrome have highlighted the link between cortisol and central obesity. However, whilst circulating cortisol levels are normal or reduced in obesity, local regeneration of cortisol, from inactive cortisone, by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) has been postulated as a pathogenic mechanism. W...

The insulin tolerance test (ITT) is used to determine the integrity of the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-somatotroph (GH) axes in patients suspected of ACTH and GH deficiency. In adults a cortisol response <500nmol/L is considered pathological and a GH peak <9mU/L is consistent with severe GH deficiency. Exercise is an alternative stimulus to GH release which may be used to diagnose GH deficiency during childhood but is rarely used during adult li...

Thyroid hormone (TH) is essential for fetal development and before 14 weeks maternal supply of TH is critical to the fetus. Subtle abnormalities of maternal thyroid status have been reported to affect neurodevelopment in childhood (1,2). To explore this further, we examined the relationship between maternal thyroid status and newborn measures of growth potential. A cohort of uncomplicated pregnant women (n=480) was recruited. At antenatal booking (mean gestation 13.05 weeks) m...

Congenital isolated ACTH deficiency (IAD) is a rare inherited disorder that is clinically and genetically heterogeneous. Patients are characterised by low or absent cortisol production secondary to low plasma ACTH despite the absence of structural pituitary defects and normal secretory indices of other pituitary hormones. When tested, there is often no ACTH response to exogenous CRH. Onset may occur in the neonatal period, but often is first observed in later childhood. Candid...

Patients with obesity are relatively Growth Hormone (GH) deficient. GH has potent effects on adipocyte biology, stimulating lipolysis but also promoting pre-adipocyte proliferation. Conversely, we have shown that cortisol inhibits pre-adipocyte proliferation and enhances differentiation. Furthermore, GH, acting through IGF-1, inhibits 11 beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) which converts the inactive glucocorticoid, cortisone (E) to active cortisol (F) in ad...