Endocrine Abstracts

Glucocorticoid metabolism is altered in a tissue-specific manner in obesity. Increased reactivation of glucocorticoids by 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1) amplifies glucocorticoid action in abdominal fat, whereas increased metabolism of glucocorticoids by hepatic A-ring reductases may contribute to activation of the hypothalamic-pituitary-adrenal axis. These changes have been characterised in leptin-resistant obese Zucker rats and obese humans. Here we inves...

A Short Synacthen Test (SST) cannot be used to assess the pituitary-adrenal axis immediately post transphenoidal adenectomy (TSA). A 9am cortisol must be used to achieve a balance between avoiding hypoadrenalism and over treating with replacement steroids. In this study we have determined the cut-off levels at which an averaged cortisol is most accurate and at which patients can be safely discharged with/without regular steroids or an emergency pack.62 patients (M:F 34:28) wit...

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activates cortisol (F) from cortisone (E). Our recent human studies identified 11beta-HSD1 to the non-pigmented layer (NPE) of the ocular ciliary epithelium, confirming that this enzyme is integral to the physiology of aqueous humour (AH) production vital for the maintenance of intraocular pressure (IOP). 11beta-HSD1 has also been implicated in the pathogenesis of obesity, and our previous data have defined this enzyme i...

The epithelial cells of the choroid plexus (CP) are responsible for cerebrospinal fluid (CSF) secretion into the ventricles of the brain, which then drains principally into the dural sinuses. The balance between production and drainage, in part, facilitates a normal intracranial pressure. The secretion of sodium and anions by the CP, creates an osmotic gradient driving the movement of water into the ventricles. This mechanism is analogous to that found in the ocular ciliary ep...

Genetic variants of the HLA class II region (DRB1, DQB1 and DQA1) and CTLA-4 contribute to susceptibility to Graves' disease (GD). Whilst disease susceptibility has been mapped to a non-coding 6.1kb 3' region of CTLA-4, the primary aetiological variants within the HLA class II region remain unknown. The aims of this study were (i) determine which of the three HLA class II loci account for the primary association with GD and (ii) examine disea...

The abundance of class 1 cytokine receptors for hepatic growth hormone (GH) and long form of prolactin (PRL) receptor peak near to term coincident with the rise in fetal plasma PRL. The extent to which maintenance of high plasma PRL may alter mRNA abundance for the GH or PRL receptors is not known. The present study aimed to determine whether chronic administration of PRL alters the hepatic GH and/or prolactin (PRL) receptor mRNA abundance in livers of 1-week-old lambs.<p ...

Metabolism of glucocorticoids to dihydro and tetrahydro derivatives via hepatic 5alpha- and 5beta-reductases has been assumed to be a pathway of irreversible inactivation of glucocorticoids. However, 5alpha-reduced metabolites of other steroids (testosterone, aldosterone) have significant affinity for the parent hormone receptor. We have investigated whether 5alpha-reduced metabolites of corticosterone (B) are GR agonists.In hepatocytes from male lean Zucker rats (n=6) com...

5beta-Reductase is a key glucocorticoid metabolising enzyme. In humans, urinary steroid metabolite profiles suggest an inverse relationship between 5beta-reductase and 11beta-hydroxysteroid dehydrogenase (11HSD1) in obesity and congenital deficiency of 11HSDs. Indeed in the obese Zucker rat hepatic 11HSD1 is decreased and 5beta-reductase increased. Here we use animal models with well characterised alterations in 11HSD1 to explore the link between these enzymes.11HSD1 was m...

Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis in men of low birthweight may be an important link between early life events and adult metabolic syndrome. In animal models females are more sensitive to HPA axis programming by manipulations in utero, but whether gender influences susceptibility in humans is unknown.We studied 106 women aged 67-78 y, from Hertfordshire UK, in whom birthweight was recorded. None had pituitary or adrenal disease or were rec...

Urine 18-hydroxy cortisol ('18OHF') measurements are claimed to have the potential to discriminate between primary hyperaldosteronism due to either Conn's syndrome/adrenal adenoma (increased values) or idiopathic adrenal hyperplasia (normal values), and also to identify cases of glucocorticoid-suppressible hyperaldosteronism ('GSH').We have evaluated three urine 18-OHF methods using a panel of samples from patients with primary hyperaldosteronism [due to either adenoma (N=...