Searchable abstracts of presentations at key conferences in endocrinology

ea0066s1.3 | Endocrine Track 1: Symposium 1 | BSPED2019

Maternal thyroid function in pregnancy and childhood outcomes

Ludgate Marian

The foetus relies on placental transfer of maternal thyroid hormones, until the thyroid matures fully, at ˜36 weeks gestation. Studies in animals, and the cognitive impairment experienced by children born in areas of iodine deficiency or to mothers with hypothyroidism, highlight the importance of thyroid hormone in brain development. The impact of less severe thyroid dysfunction remained controversial until two large-scale trials investigated the effect on child IQ of thy...

ea0059s7.3 | The microbiome in endocrine disease | SFEBES2018

A Role for the Microbiome in Graves’ Disease and Orbitopathy?

Ludgate Marian

In Graves’ disease (GD) thyrotropin receptor (TSHR) stimulating autoantibodies cause hyperthyroidism. Many GD patients develop Graves’ orbitopathy (GO) characterized by orbital tissue remodelling including adipogenesis. Whilst progress has been made in understanding the processes causing expansion of orbital tissues, little is known about loss of tolerance to the TSHR target autoantigen. Mechanisms for triggering autoimmunity by microorganisms include molecular mimic...

ea0094s5.1 | Graves' disease – Understanding the cause and dealing with the consequences that matter | SFEBES2023

Thyrotropin receptor autoantibodies, stimulating, blocking or neutral

Ludgate Marian

Graves’ disease (GD) is caused by autoantibodies to the thyrotropin receptor (TSHR) which mimic the action of TSH. Thyroid stimulating antibodies (TSAB) predominantly signal via the cAMP/PKA cascade whilst blocking antibodies (TBAB) prevent TSH binding. Flow cytometry reveals TSHR antibodies which bind the receptor but do not activate cAMP or inhibit TSH binding. These ‘neutral’ antibodies were identified in people with euthyroid Graves’ orbitopathy (GO, ey...

ea0021p179 | Diabetes and metabolism | SFEBES2009

Functional muscarinic acetylcholine receptors are expressed in white and brown adipose tissue

Stephens Mark , Rees Aled , Ludgate Marian

Both brown (BAT) and white (WAT) adipose tissue have neuroanatomically well characterized sympathetic innervation (with activation initiating lipid mobilization), but little evidence to support the presence of a (putatively counter-regulatory) parasympathetic input.Parasympathetic actions are mediated through muscarinic acetylcholine receptors (mAChR). The mouse 3T3-L1 (white fat-derived) cell line expresses M1, M3 and M4 mAChR during differen...

ea0013p151 | Diabetes, metabolism and cardiovascular | SFEBES2007

Comparison of the effects of cannabinoid receptor modulation in human primary preadipocytes and a murine cell line

Agarwal Neera , Rees Aled , Ludgate Marian

Background and Objective: CB1 antagonism may have potential benefits in the metabolic syndrome, with effects mediated through central orexigenic mechanisms and peripheral action on adipose tissue. We have previously described the effects of CB1 activation/inactivation on murine white preadipocyte 3T3-L1 proliferation; we now extend these studies to human tissue.Method: Ethical approval was obtained for this study. Human preadipocytes were isolated from w...

ea0059oc1.3 | Translational highlights | SFEBES2018

Novel insights into the genetic architecture of thyroid disease

Taylor Peter , Anney Richard , Dayan Colin , Ludgate Marian , Rees Aled

Introduction: There has been a substantial increase in our knowledge of the genetic architecture of thyroid function, with numerous variants associated with TSH and/or FT4 levels. However, our knowledge of the genetic variants associated with thyroid disease is more limited.Methods: Data was obtained from the Neale laboratory† which provided a case-control study to identify single nucleotide polymorphisms associated with a diagnosis of hypothyroidi...

ea0015p142 | Diabetes, metabolism and cardiovascular | SFEBES2008

Adipose: depot specific differences in response to TSH receptor activation: role of the extra-cellular matrix

Zhang Lei , Webber Jason , Steadman Robert , Ludgate Marian

Thyrotropin receptor (TSHR, signals via CREB) expression increases during adipogenesis, a process occurring in Graves’ orbits. CREB activation has been reported ‘necessary and sufficient’ to induce adipogenesis. However, we previously demonstrated that expression of constitutively active TSHR in orbital preadipocytes stimulated early but inhibited later differentiation stages, even when PPARγ agonist induced. Overproduction of proteoglycans is also a featur...

ea0015p146 | Diabetes, metabolism and cardiovascular | SFEBES2008

Comparison of the effects of cannabinoid receptor modulation on adipogenesis in human primary preadipocytes and a murine cell line

Agarwal Neera , Rice Samuel , Zhang Lei , Rees Aled , Ludgate Marian

Background: CB1 antagonism has potential benefits in the metabolic syndrome, with effects mediated through central orexigenic mechanisms and peripheral action on adipose tissue. We have previously demonstrated the inhibitory effects of CB1 inactivation on preadipocyte proliferation and now extend these studies to in vitro adipogenesis.Aims: To compare the effects of CB1 agonism and antagonism on differentiation in both preadipocyte cell lines and ...

ea0015p148 | Diabetes, metabolism and cardiovascular | SFEBES2008

Thyrotropin receptor activation and preadipocyte biology; dissecting the effects of Gsα and Gβγ signalling on 3T3-L1 preadipocytes

Zhang Lei , Paddon Carol , Grennan-Jones Fiona , Ludgate Marian

TSH receptor (TSHR) expression increases >100-fold during adipogenesis and signals via CREB. Since CREB activation has been reported to be ‘necessary and sufficient to induce adipogenesis’, we investigated whether TSHR activation, a feature of most thyroid dysfunction, has a role in adipocyte biology and evaluated the contribution of Gsα and Gβγ signalling.Retroviral vectors for WT or constitutively active mutant TSHR* or ...

ea0031p38 | Clinical biochemistry | SFEBES2013

Development of an inductively coupled plasma-mass spectrometry method for measurement of urine iodine and assessment of iodine status in subclinical hypothyroidism

Jones Katie , Rogers Joanne , De Lloyd Anna , Rees Aled , Ludgate Marian , Evans Carol

Iodine deficiency may lead to reduced thyroid hormone production and ultimately hypothyroidism. The UK has previously been considered to be iodine sufficient, however recent evidence suggests the UK may be iodine deficient. Iodine status can be assessed in several ways, including measurement of urinary iodine excretion, for which inductively coupled plasma-mass spectrometry (ICP-MS) is considered the gold standard method.An ICP-MS method for determinatio...