Endocrine Abstracts

Hypospadias is among the most common congenital malformations with a mean prevalence of 19.9 per 10,000 live births in Europe. The cause of many cases of hypospadias remains unclear but likely results from a combination of genetic susceptibility and environmental factors. Although rodent studies have provided great insights into external genitalia morphogenesis, extrapolations to the human genitals is challenging given significant anatomic and morphogenetic differences. With t...

Inadequate dietary iodine intake is the most common cause of preventable mental impairment worldwide and is defined by the WHO as a population median urinary iodine (UI) excretion <100 μg/l. No contemporary data are available for the UK according to the ICCIDD. The UK has no programme of food/salt iodination.We have performed a systematic assessment of the current UK iodine status in 14–15 years old schoolgirls. Seven hundred and eighty-fiv...

Synthetic glucocorticoids bind to the glucocorticoid receptor (GR) and have been used for nearly 70 years to treat inflammatory diseases. However, their use is limited by adverse effects such as diabetes, muscle wasting and osteoporosis. High throughput screening identified a novel non-steroidal scaffold with great potential for chemical optimization. Through rational design we developed the indazole ether series which combines high potency with structural motifs that provide ...

T3 is an important regulator of skeletal development and adult bone maintenance. Thyroid hormone action requires efficient transport of T4 and T3 into target cells. We hypothesized that monocarboxylate transporter-8, encoded by Mct8 on the X-chromosome, is an essential thyroid hormone transporter in bone. To test this hypothesis, we determined the juvenile and adult skeletal phenotypes of male Mct8 knockout mice (Mct8KO) and Mct8D1D2KO compo...

Iodine is a trace element required for thyroid hormone production. Requirements increase in pregnancy, when even mild deficiency may affect offspring neurocognitive development.The gold standard for assessing iodine status is population surveys of urinary iodine concentration (UIC). The WHO also suggests a population prevalence of >3% of TSH values > 5 mIU/L indicates deficiency. A recent UK survey of 700 teenage girls demonstrated ...

T3 is an important regulator of skeletal development and adult bone maintenance. Thyroid hormone action requires efficient transport of T4 and T3 into target cells. We hypothesized that monocarboxylate transporter-8, encoded by Mct8 on the X-chromosome, is an essential thyroid hormone transporter in bone. To test this hypothesis, we determined the juvenile and adult skeletal phenotypes of male Mct8 knockout mice (Mct8KO) and Mct8D1D2KO compo...

Iodine is a trace element required for thyroid hormone production. Requirements increase in pregnancy, when even mild deficiency may affect offspring neurocognitive development.The gold standard for assessing iodine status is population surveys of urinary iodine concentration (UIC). The WHO also suggests a population prevalence of >3% of TSH values > 5 mIU/L indicates deficiency. A recent UK survey of 700 teenage girls demonstrated ...

Background: Obesity exacerbates a number of chronic inflammatory diseases including asthma, with increasing adiposity observed to worsen asthma severity and disease control. This exacerbation may arise as gut-derived bacterial fragments (endotoxin) and associated markers of endotoxin (lipopolysaccharide binding protein (LPB)), enter the circulation through a damaged gut barrier, provoking systemic inflammation. This study investigated the role of body weight on gut permeabilit...

Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant disorder characterized by lifelong elevation of serum calcium concentrations with inappropriately low urinary calcium excretion. Three types referred to as FHH1, FHH2 and FHH3 and located on chromosomes 3q21.1, 19p and 19q13.3, respectively, have been reported. FHH1, caused by loss-of-function mutations of the calcium-sensing receptor (CaSR), accounts for >65% of FHH patients. To identify the gen...

Hypothyroidism and thyrotoxicosis have detrimental effects on skeletal development and adult bone strength. These effects result from thyroid hormone actions in bone, although a direct role for TSH in osteoblasts and osteoclasts was postulated following analysis of TSH receptor (TSHR) null mice. This hypothesis remains controversial as other studies failed to demonstrate osteoblast or osteoclast responses to TSH in vitro. Thyrostimulin is a heterodimeric glycoprotein ho...