Searchable abstracts of presentations at key conferences in endocrinology

ea0031oc2.1 | Steroids and thyroid | SFEBES2013

Loss-of-function mutations in IGSF1 cause a novel, X-linked syndrome of central hypothyroidism and testicular enlargement

Schoenmakers Nadia , Sun Yu , Bak Beata , van Trotsenburg Paul , Oostdyk Wilma , Voshol Peter , Persani Luca , Davis Timothy , le Tissier Paul , Gharavy Neda , Appelman-Dijkstra Natasha , Pereira Alberto , den Dunnen Johan , Breuning Martijn , Hennekam Raoul , Chatterjee V Krishna , Dattani Mehul , Bernard Daniel , Wit Jan-Maarten

Introduction: Congenital central hypothyroidism occurs either as isolated TSH deficiency or in conjunction with other pituitary hormone deficits. Undetected central hypothyroidism is associated with developmental delay in children and adverse cardiometabolic sequelae in adults. Hitherto, mutations in the TRH receptor (TRHR) or TSHβ subunit (TSHB) genes are the only known causes of isolated TSH deficiency.Methods: Using whole exome and candidate gene...

ea0031p293 | Pituitary | SFEBES2013

Pulsatile GnRH signaling to ERK: relevance of pulse duration and frequency

Perrett Rebecca , Armstrong Stephen , Fowkes Rob , McArdle Craig

GnRH is secreted in pulses and its effects on pituitary gonadotropes depend on pulse frequency. This is crucial for physiological control and therapeutic manipulation of the system (in IVF and treatment of hormone-dependent cancers) but GnRH pulse frequency decoding mechanisms are unknown. The simplest form of frequency dependence is a linear relationship between integrated inputs and outputs but such ‘integrative tracking’ cannot explain the bell-shaped frequency-re...

ea0029gh1biog | The Geoffrey Harris Prize Lecture | ICEECE2012

The Geoffrey Harris Prize Winner

Jonathan R Seckl

Professor Jonathan R Seckl, UK AbstractThis prestigious prize is intended for established workers in the field of basic and clinical neuroendocrinology and is generously supported by Ipsen. This year’s recipient is Professor Jonathan R Seckl. The prize will be presented as part of the ICE/ECE 2012 opening ceremony where Prof. Seckl will deliver his lecture. Prof. Seckl will also deliver two other l...

ea0029s1.2 | Molecular mechanisms of differentiated thyroid cancer | ICEECE2012

Correlation between the BRAF V600E mutation, TGFβ pathway and tumour invasiveness in papillary thyroid carcinomas

Riesco-Eizaguirre G. , Santisteban P.

The V600E mutation of BRAF oncogene is one of the most frequent genetic events in thyroid cancer, particularly in papillary thyroid carcinomas (PTC) and in some anaplastic carcinomas that derive from preexisting PTC. It has been associated with advanced clinical stages, extrathyroidal extension, and a high risk of recurrences, particularly those that have lost the ability to accumulate iodide, a property mediated by the sodium iodide symporter (NIS).Our ...

ea0029oc13.3 | Adrenal Basic | ICEECE2012

Cortisol secretion is dependent on intraadrenal production of ACTH in macronodular bilateral adrenal hyperplasia causing Cushings syndrome

Louiset E. , Duparc C. , Young J. , Boutelet I. , Renouf S. , Bram Z. , Groussin L. , Caron P. , Tabarin A. , Grunenberger F. , Christin-Maitre S. , Kuhn J. , Anouar Y. , Bertherat J. , Lefebvre H.

Illicit expression of membrane receptors for circulating regulatory factors, such as gastric inhibitory polypeptide (GIP), luteinizing hormone (LH) and serotonin (5-HT) receptors, has been well documented in ACTH-independent macronodular adrenal hyperplasias (AIMAHs) causing Cushing’s syndrome. In addition, we have observed an abnormal expression of ACTH in some steroidogenic cells in two AIMAH tissues. The aim of the present study was to investigate the role of local pro...

ea0029p332 | Cardiovascular Endocrinology and Lipid Metabolism | ICEECE2012

Sympathetic over-activity and low adrenocortical responses to hypoglycemia in patients in early stage of hypertension

Penesova A. , Radikova Z. , Cizmarova E. , Kvetnansky R. , Vlcek M. , Imrich R.

Increased activity of sympathetic nervous system (SNS) was observed in early stage of hypertension onset. The aim of our present study was to estimate catecholamines response to stress stimulus (insulin induced hypoglycaemia) in young males with early diagnosed non-treated hypertension grade 1 (HT) and normotensive controls (NT).Methods: Insulin tolerance test (ITT, 0.1 IU/kg body weight, Actrapid HM, i.v.) was performed in 21 HT male subjects aged 20.0&...

ea0029p785 | Endocrine tumours and neoplasia | ICEECE2012

Mitochondrial respiratory chain defects: a novel molecular mechanism of Mitotane for treatment of Adrenocortical Carcinoma

Hescot S. , Slama A. , Paci A. , Remy H. , Chadarevian R. , Trabado S. , Lombes A. , Young J. , Baudin E. , Lombes M.

Mitotane (o,p’DDD) represents the most effective treatment of adrenocortical carcinoma (ACC). However, molecular mechanisms of mitotane action remain poorly understood. Mitochondrial (mt) impact of mitotane has previously been suggested but not yet fully validated. We investigated functional consequences of mitotane exposure on mitochondrial steroidogenesis, respiratory chain activity and biogenesis, using human adrenocortical secreting H295R and non-secreting SW13 cells....

ea0029p1557 | Steroid metabolism + action | ICEECE2012

Unconjugated steroids and steroid sulfates in maternal blood show comparable predictivity for assessment of gestational age from the 28th to 41st week of pregnancy

Kancheva L. , Hill M. , Kanceva R. , Parizek A. , Starka L.

Recently we demonstrated a close correlation between the gestational age (GA) and steroid metabolome in maternal and fetal body fluids using multivariate models including both unconjugated (n=39) and conjugated steroids (n=30) that were measured by GC-MS method including two separate multicomponent analyses (for unconjugated steroids and steroid polar conjugates). We focused on the comparison of the predictive value of the levels of unconjugated steroids alone, c...

ea0029p1560 | Steroid metabolism + action | ICEECE2012

Physiological relevance of peripherally produced gabaergic and glycinergic steroids in human late pregnancy and around parturition

Hill M. , Parizek A.

Although neuroactive steroids are well characterized, their physiological relevance in human pregnancy remains indecisive. Hence, we attempted to derive this information from the combination of our metabolomic data, pharmacological data found in the literature and knowledge contained in gene expression databases. These results indicate that GABAergic steroids influence maternal CNS but have limited effect in the fetal brain and maternal and fetal periphery, partly because of t...

ea0029p1586 | Thyroid (non-cancer) | ICEECE2012

Endocrine bioengineering: reconstruction of a bioartificial thyroid lobe using its natural, three-dimensional (3D) stromal / vascular matrix as a scaffold

Strusi V. , Zini N. , Dallatana D. , Mastrogiacomo S. , Parrilli A. , Giardino R. , Lippi G. , Spaletta G. , Bassoli E. , Gatto A. , Iafisco M. , Sandri M. , Tampieri A. , Toni R.

To test the feasibility of reconstructing ex situ an entire bioartificial thyroid gland suitable for transplantation we have bioengineered a rat thyroid lobe using its decellularized stromal / vascular matrix, eventually 3D recellularized with thyroid stem / precursor cells. Sprague-Dawley male rats (220–240 g) were used as thyroid donors, and lobe matrixes obtained by freezing / detergent / enzyme processing. Test matrixes were made electrondense and analyzed by m...