Endocrine Abstracts

In addition to its central role in the control of thyrocyte growth and function, the TSHR is expressed during the differentiation of mesenchymal precursors. To explore further, we have developed an in vitro model in which TSHR activation is achieved by introducing constitutively active (M453T, L629F) TSHR, using retroviral vectors.We aimed to investigate the effect of TSHR activation on body composition, via the production of TNFα and express...

Objectives: While evidence for an increased risk of hypertension in both overt hyperthyroidism and overt hypothyroidism is consistent, the relation between subclinical hyperthyroidism and blood pressure has not yet received sufficient attention. We aimed to investigate possible associations of decreased serum thyrotropin levels and subclinical hyperthyroidism with blood pressure, pulse pressure, and the risk of hypertension.Design: The population-based c...

Progressive osseous heteroplasia (POH, MIM 166350) is a rare autosomal dominant disorder characterised by extensive dermal ossification during childhood, followed by widespread heterotopic ossification of skeletal muscle and deep connective tissue. Recently, genetic basis was found to be common with Albright’s hereditary osteodystrophy (AHO) (Shore et al., 2002): paternally inherited inactivating mutations of the GNAS1 gene were found. GNAS1 is the ge...

By including the synthetic glucocorticoid (GC), dexamethasone, in the maternal drinking water on gestational days 16–19 (0.5 μg/ml) or days 1–7 after birth (1.0 μg/ml), we have recently demonstrated (McArthur et al. J. Neuroendocrinol. 17: 475) that perinatal exposure of rat pups to GCs increased dopaminergic (DA) cell numbers in the adult ventral tegmental area (VTA) at −5.1 to −5.4 mm relative to Bregma (level I). In order to investig...

Introduction: Testicular germ cell tumours are the most frequent cancer of young men. Epidemiological and clinical data have suggested that fetal or perinatal exposure to environmental endocrine disruptors (EEDs) with estrogenic effects, could participate to testicular germ cell carcinogenesis. However, EEDs (like bisphenol A (BPA) are often weak ligands for classical nuclear estrogen receptors.Using a human seminoma cell line (JKT-1), devoid of ERα...

The calcium-sensing receptor (CaSR) belongs to family C of G-protein coupled receptors (GPCRs) that bind glutamate, GABA, taste molecules and pheromones. Loss-of-function mutations of the CASR gene located on chromosome 3q21–24, cause familial benign hypocalciuric hypercalcaemia type 1 (FBHH1). The genes causing FBHH2 and FBHH3, whose chromosomal locations are on 19p and 19q13.3, respectively, remain unknown. FBHH3, sometimes called the Oklahoma variant (FBHHO...

By direct measurement of muscle sympathetic nerve activity (MSNA) we previously demonstrated a markedly decreased adrenergic tone in newly diagnosed acromegalic patients. The present study was aimed at confirming this finding in a larger group of patients and establishing the pathophysiological role of insulin resistance, GH and IGF1 levels, circulating leptin and extracellular water (ECW) in this abnormality.Study design: Fifteen de novo patients...

The Thyrotropin receptor (TSHR) is known as the important key-player for regulation of thyroid growth and function. As a G-protein coupled receptor (GPCR) TSHR predominantly activates the Gs/adenylyl cyclase and the Gq/11 phospholipase C signaling pathways, that finally regulate thyroid hormone production. Aberrant thyroid hormone production can be caused by activating TSHR mutations in case of toxic thyroid nodules or non-autoimmune hyperthyroidism or via inactivating mutatio...

Case: A 44-year-old lady was diagnosed with Acromegaly (IGF-1 of 1315 ng/ml, prolactin 498 mu/l). She was also thyrotoxic clinically and biochemically with T4 29 pmol/l (normal 9-26), total T3 3.24 nmol/l (normal 0.9–2.2) but high TSH of 3.50 mu/l (normal 0.35–3.5). Further work-up with TRH testing and α-subunit measurement confirmed a TSHoma. Pituitary MRI scan showed a macroadenoma displacing optic chiasm and extending into cavernous sinu...

The pharmacology and function of G protein-coupled receptors (GPCRs) is frequently studied following expression of a single receptor in heterologous cell lines. However, many GPCRs are co-expressed. We wished to investigate how expression of pairs of receptors might modulate their function. Using a Human Embryonic Kidney 293 cell line in which the CB1 cannabinoid receptor was expressed constitutively and in which varying levels of expression of the orexin-1 receptor could be i...