Endocrine Abstracts

T3 regulates bone development and its actions are mediated by TRα and TRβ. Using TR knockout mice we demonstrated that TRα1 is the predominant mediator of T3 action in bone, although TRα2 (a non-T3 binding isoform of unknown function) and TRβ1 are also expressed in the skeleton. We show that mice lacking TRα2 have characteristic skeletal abnormalities of delayed closure of the skull sutures, abnormal clavicle development and reduced bone mineraliz...

Our initial studies suggested that plurihormonal cells are constantly found in early embryonic stages of human pituitary but are very rare later.Aim: A quantitative evaluation and morphological characterization of these plurihormonal cells.Methods: Pituitaries from therapeutically aborted human fetuses of 8–24 weeks, gestational age were fixed (with ethical permission) by immersion in 4% buffered formaldehyde. One-μm-thic...

Thyroid hormones stimulate bone formation and linear growth in children. Paradoxically, childhood thyrotoxicosis causes short stature and craniosynostosis due to early closure of the growth plates and skull sutures. In adults, however, thyroid hormone excess increases bone turnover and results in progressive bone loss and osteoporosis. Activating mutations of fibroblast growth factor receptor-3 (FGFR3) cause achondroplastic dwarfism and we have shown that T3 augments FGFR sign...

T3 is essential for skeletal development and T3-actions in bone are mediated mainly by the nuclear receptor TRα1. We previously identified that FGFR1 is a T3-responsive gene in osteoblasts by subtraction hybridization. In mice that harbor a dominant negative mutation PV, FGFR1 mRNA expression is reduced in TRα1PV mutants that exhibit skeletal hypothyroidism and increased in TRβPV/PV mice with skeletal thyrotoxicosis. In this study, primary ...

Objectives: Food intake is centrally regulated in hypothalamic nuclei where many G-protein-coupled receptors (GPCRs) are expressed which are known to be involved in weight regulation. Peripheral hormonal signals activate their corresponding receptors in the arcuate nucleus. Orexigenic signals activate POMC expression in one subset of neurons and inhibit AgRP and NPY expression in a second subset. Cleavage products of POMC, α- and β-MSH then stimulate melanocortin-4-r...

Objectives: Somatostatin (SST) inhibits glucagon and insulin secretion. Five receptor subtypes for SST are known (SSTR1-SSTR5), all of which are expressed in the endocrine pancreas. SSTR2 inhibits glucagon secretion in vitro, however its role in vivo is not well understood. Here, we characterize the role of SSTR2 in regulating glucose homeostasis in mice with diet-induced obesity.Methods: SSTR2-deficient (SSTR2−/−) and control mice...

Recent studies suggest TSH inhibits bone remodeling, indicating that TSH deficiency rather than thyroid hormone excess could cause bone loss in thyrotoxicosis. The findings predict that TSH receptor (TSHR) stimulating antibodies (TSHRAb) should inhibit bone turnover, whereas Graves’ disease patients exhibit high bone turnover with increased fracture susceptibility. We characterized TSH-action in primary human and mouse osteoblasts and osteoclasts, and explored whether a p...

T3-receptor alpha (TRa) is the predominant TR isoform in bone. To investigate its function, we analysed mice harbouring a dominant negative R384C mutation in TRa1 (TRa1m/+). The homozygous TRa1m/m mutation is lethal whereas heterozygotes are euthyroid displaying only transient postnatal hypothyroidism. Critically, dominant negative activity of the mutation is overcome by a 10-fold increase in T3, which is achieved by crossing TRa1m/+ mutants wi...

In developmental studies of mice lacking T3-receptor alpha (TRa0/0) and beta (TRb−/−) we demonstrated delayed endochondral ossification, reduced mineralisation and short stature in TRa0/0 mice, despite euthyroidism. In contrast, TRb−/− mice, which display thyroid hormone resistance with elevated T4 and T3 levels, have advanced ossification, increased mineralisation and accelerated growth. T3-target gene studie...

In 1984 an 18-year-old girl was operated because of primary hyperpara-thyroidism (PHPT). Recurrence was seen 13 years later and another neck exploration was performed. Histological examination was consistent with both adenoma and hyperplasia.She had a history of urticaria pigmentosa since the age of one year. In 1991–94 she complained of syncope, weight loss, diarrhoea, abdominal pain and alcohol intolerance. Typical skin lesions were found. Total 2...