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...

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...

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...

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...

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...

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 ...

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 ...

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...

Expansion of the orbital contents, by adipogenesis and hyaluronan (HA) overproduction, causes Graves orbitopathy (GO). Orbital HA is generated predominantly by hyaluronan synthase 2 (HAS2) whose transcription is positively regulated by pAkt in cell lines. GO is most frequently associated with Graves’ disease (GD) in which thyroid stimulating antibodies bind the TSH receptor (TSHR) increasing cAMP. Previous studies highlight a role for TSAB and ‘neutral’ TSHR ant...