Endocrine Abstracts

We have studied 20 patients with autoimmune hypothyroidism on large doses of daily thyroxine that were referred to our departments with concerns regarding possible thyroxine malabsorption or compliance issues. Here we describe 3 patients seen in Oxford. One patient had coeliac disease. The other two patients had no history of malaborption and were coeliac antibody negative. None of the 3 patients were on medication which would interfere with thyroxine absorption. All were fema...

Glucocorticoid (GC) hormone action can be modulated at the pre-receptor level by the endoluminal enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1). 11βHSD1 is a bidirectional enzyme that primarily acts as an oxo-reductase in vivo, converting the pro-hormone cortisone to its active form cortisol, while its dehydrogenase activity results in inactivation of cortisol to cortisone. 11βHSD1 oxo-reductase activity allows GC reactivation in a tissue s...

The metabolism of glucocorticoids within adipose tissue, by the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1), is known to be altered in obesity and following high fat feeding. Until recently, little attention has been paid to the fat depots found directly adjacent to blood vessels. Emerging evidence suggests that perivascular adipose may play a key role in modulating vascular function. The presence of steroidogenic enzymes within perivascular adipose, and the eff...

Disorders of male reproductive health, including testicular cancer, cryptorchidism, hypospadias and low sperm counts, are common and may be increasing in incidence. These conditions manifest at different life stages (low sperm counts and testicular cancer in adulthood; cryptorchidism and hypospadias at birth) but are proposed to originate in fetal life. These disorders have therefore been hypothesized to comprise a ‘testicular dysgenesis syndrome’ (TDS), which result...

Ion and fluid transport mechanisms within the eye are important for several key physiological processes including the maintenance of corneal transparency and the regulation of intraocular pressure (IOP). The mechanism involved in epithelial sodium transport in the eye is regulated by corticosteroids and at a pre-receptor level, by 11β-hydroxysteroid dehydrogenase (11β-HSD) activity. Recent studies localised type 1 (11β-HSD1), an oxo-reductase that activates cort...

Bile acids inhibit glucocorticoid and mineralocorticoid metabolism. However bile acids may also influence hormone action by modulating steroidogenesis in the adrenal gland. In rodents adrenal cholesterol supply for steroidogenesis is derived from circulating HDL through the actions of scavenger receptor SR-B1. Since hepatic SR-B1 expression is known to be regulated by bile acids, we have investigated whether adrenal SR-B1 is similarly affected and, if so, whether adrenal lipid...

Mifepristone (RU38486) is a progesterone and glucocorticoid receptor antagonist which is used clinically to induce medical abortion, and as a research tool, e.g., in metabolic syndrome and depression. We aimed to develop a sensitive method to detect and quantify mifepristone in human plasma.Analyses were developed using a Surveyor HPLC system, with a mobile phase of methanol:ammonium acetate (5 mM) (70:30; 0.4 ml/min) and a C18 column (5 μm; 2.1&#21...

The effect of growth hormone (GH) replacement on thyroid function in hypopituitary patients has only been studied in small groups of children and adults with conflicting results.We aimed to define the effect and clinical significance of adult GH replacement on thyroid status in a large cohort of 243 patients with hypopituitarism due to various causes. 84 patients were considered euthyroid before GH treatment and 159 patients had central hypothyroidism an...

In humans, glucocorticoids (GC) are implicated in the pathogenesis of obesity and insulin resistance. GCs are regulated at the prereceptor level by 11beta-HSDs. 11beta-HSD1 predominately displays oxo-reductase activity (cortisone/11-dehydrocorticosterone to cortisol/ corticosterone), requiring the cofactor NADPH. Recently, studies in humans have shown that the enzyme H6PDH, by generating NAPDH in the endoplasmic reticulum (ER) is crucial for oxo-reductase activity. This study ...

We have reported that serum DHEAS increases in growth hormone deficient (GHD) adults with intact ACTH reserve during GH replacement (GHR) in contrast with persisting low levels in ACTH-deficient GHD patients (Isidori et al. Clin Endo 2003:58:601). This was associated with a lower GH dose requirement in ACTH sufficient patients suggesting that DHEA may augment IGF-I generation. We have examined this hypothesis in a double blind placebo controlled trial of 30 hypopituitary femal...