Endocrine Abstracts

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...

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...

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...

An established murine model of thyroid eye disease is induced by transfer of thyrotropin receptor (TSHR) primed T-cells to syngeneic recipients. Our aim was to extend the model to determine if: there are gender differences, Rundle's curve occurs and magnetic resonance imaging (MRI) could be applied as an in vivo marker. Orbital MRI on non-living mice used a surface coil and 1.5T MRI. 0.75mm slices have resolution sufficient to image ocular muscles. TSHR primed T-cells were gen...

Does Iodide Modulate The Biological Outcome of Activating Thyrotropin Receptor Mutations?Dr. F. Al-Khafaji and Dr. M. LudgateHyperthyroidism is caused by pathogenic activation of the thyrotropin receptor (TSHR) either by the thyroid stimulating antibodies of Graves' disease (GD) or activating TSHR mutations. These produce nodular goitre or familial hyperthyroidism. The pathogenic mechanism predominating varies according to the iodide intake, with nodular goitre account...

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...

The rising prevalence of type 2 diabetes can be directly related to increasing levels of population obesity and associated insulin resistance. Adipose tissue has neuroanatomically well characterized sympathetic innervation (with activation initiating lipid mobilization), but little evidence to support the presence of a (putatively counter-regulatory) parasympathetic input (Bartness & Song 2007). Parasympathetic actions are mediated through muscarinic acetylcholine receptor...

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...

BackgroundCannabinoid (CB) receptors are expressed in adipocytes. CB1 antagonism may have potential in the metabolic syndrome, with effects mediated through central orexigenic mechanisms and via peripheral action on white adipose tissue (WAT). Equivalent studies in brown adipose tissue (BAT) are lacking.ObjectiveWe aimed to compare CB1 and CB2 receptor expression during WAT and BAT adipogenesis and to investi...

Hyperthyroidism is a common disorder, most usually caused by Graves' Disease (GD), in which thyroid-stimulating antibodies (TSAB) mimic thyrotropin. Since the diagnosis of GD is made clinically and its signs and symptoms are indistinguishable from those of patients harboring an activating germline thyrotropin receptor (TSHR) mutation, incorrect diagnoses have been made. Point mutations in more than 30 residues, predominantly in exon 10, of the TSHR cause constitutivity making ...