Endocrine Abstracts

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...

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...

The number of patients treated for malignant disease in childhood surviving into adulthood is increasing, but success is tempered by long-term side-effects of chemotherapy and radiotherapy; 40% develop one or more endocrinopathy. ALL is a common childhood malignancy treated with chemotherapy and cranial irradiation. The latter causes anterior pituitary hormone deficiencies, most frequently GH deficiency.We have determined GH status in 13 patients treate...

11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) is responsible for the conversion of hormonally active cortisol (F) to inactive cortisone (E), and is expressed in mineralocorticoid target tissues (kidney, colon). However, the most abundant source of this enzyme is human placenta, notably placental trophoblast where it is thought to protect the fetus from maternal hypercortisolaemia and play a role in fetal growth and development. During gestation placental trophobla...

Central obesity is associated with increased morbidity and mortality. Pre-adipocyte proliferation and differentiation contribute to increases in adipose tissue mass, yet the mechanisms that underpin these processes remain unclear. Patients with glucocorticoid excess develop central obesity, but circulating cortisol levels in idiopathic obesity are normal. The enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts inactive cortisone (E) to active cortisol (F)...

The key enzymes in the terminal stages of human adrenal gland corticosteroid biosynthesis are aldosterone synthase (AS) and 11beta-hydroxylase (11beta-OHase). Their amino acid sequences differ by only 7% but they exhibit markedly different enzymatic activities. AS is expressed solely in the zona glomerulosa and converts 11-deoxycorticosterone (DOC) to aldosterone whereas 11beta-OHase is expressed mainly in the zona fasciculata and produces cortisol from 11-deoxycortisol. The 3...

Volume 82, Issue 1, January 2015, Pages 2–11. DOI: 10.1111/cen.12603...

Polycystic ovary syndrome (PCOS) is a triad of insulin resistance, hyperandrogenism and anovulation. PCOS is associated with increased adrenocortical drive, which may have adverse metabolic consequences. Here we analysed the relationship of urinary androgen and glucocorticoid metabolite excretion with insulin resistance in a large PCOS cohort.We compared results from 127 PCOS patients (Rotterdam criteria) with 100 BMI-matched controls. All subjects under...

Osteosarcoma (OS) is an aggressive malignant tumour of osteoblasts occurring predominantly in children and young adults. Despite chemotherapy relapse is common and mortality remains ~50%. Non-transformed osteoblasts are highly sensitive to glucocorticoids which reduce proliferation and induce apoptosis. Previously, we observed that OS cells, but not normal osteoblasts, express 11beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2). This enzyme powerfully inactivates cortis...

Non alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. The potential role of glucocorticoids (GC) in the pathogenesis of NAFLD, is highlighted by patients with GC excess, Cushing’s syndrome, who develop central adiposity, insulin resistance and in 20% of cases, NAFLD. Although in most cases of NAFLD, circulating cortisol levels are normal, hepatic cortisol availability is controlled by enzymes that regenerate cortisol from inacti...