Endocrine Abstracts

Oestrogen receptor (ER) activity has a wide spectrum of functions in the human body, including the development, growth and maintenance of the reproductive system. There are two ER subtypes, ERα and ERβ. The latter exists as multiple splice variants (ERβ1, ERβ2 and ERβ5) some of which lack a steroid ligand-binding domain. ERs act as steroid-ligand activated transcription factors. Epidermal growth factor (EGF) acting via the MAP kinase pathway has been s...

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...

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 ...

Neoplastic thyroid diseases (multinodular goiter (MNG), follicular adenoma, differentiated (DTC) and undifferentiated thyroid carcinoma) have a higher incidence in women than in men. In fact, in the last ten years, DTC is the only cancer increasing the frequency in women, with an incidence similar to ovarian carcinoma or lymphomas.TGFb is a secreted factor important in the normal function of the thyrocyte. It has two independent actions: a fast antiproli...

One possible route for treating type 1 diabetes is through an induced augmentation of beta cell mass. Some success has been achieved in recent years using islet grafts into the liver but at present the main limitation to the wider application of this technique is the limited supply of islets from human organ donors. To overcome this problem, alternative sources of β-cells need to be found. One approach is via transdifferentiation, or the conversion of one cell type...

Rapid activation of diverse signal transduction pathways is thought to play an integral role in the cellular responses to many steroid hormones, including progesterone. This sex steroid is essential for normal reproduction in nearly all species. The recent cloning of a G-protein coupled receptor with the properties of a membrane progestin receptor (mPR) in fish and the subsequent identification of three mammalian homologues (mPR-alpha, -beta, and -gamma) raised the possibility...

Adipogenesis is induced when intracellular cAMP increases and follows cell cycle arrest. During preadipocyte differentiation expression of the TSHR, which signals via cAMP and the inositol phosphate cascade, is upregulated. To investigate the role of TSHR activation in adipogenesis, we have developed an in vitro model in which constitutively active TSHR mutants (L629F, M453T) are introduced by retroviral vectors (RV).We aimed to compare the effect...

The TSHR is expressed during adipogenesis. We have employed in vitro models to investigate how TSHR activation affects this process. Gain-of-function TSHR mutants were introduced into preadipocytes using retroviral vectors. We have demonstrated that TSHR activation inhibits their proliferation and PPAR-gamma agonist (pioglitazone) induced adipogenesis. The aim of this study was to investigate the mechanisms operating.Non-modified primary human preadipocy...

Glucocorticoid sensitivity is dependent on the intracellular concentration of the glucocorticoid receptor (GR). GR expression is regulated in a complex, cell-type specific manner, but in most cell types the GR is subject to negative autoregulation by glucocorticoid exposure. Many human diseases are associated with reduced tissue sensitivity to glucocorticoids, including inflammatory arthritis, asthma, and chronic obstructive pulmonary disease. Therefore there is interest in ap...

3beta-hydroxysteroid dehydrogenase (3beta-HSD) expression is essential for the synthesis of all classes of steroid hormones, converting delta5-3beta-hydroxysteroids into hormonally active delta4-3-ketosteroids in NAD+-dependent reactions. A variety of 3beta-HSD isoforms have been described in primate, rodent and other mammals, often exhibiting distinct kinetic properties, preferential subcellular localization, as well as alternative substrate s...