Searchable abstracts of presentations at key conferences in endocrinology

ea0035p334 | Developmental Endocrinology | ECE2014

Physiological expression of thyroid hormone receptors during zebrafish development and effects of their molecular disruption

Marelli Federica , Persani Luca

Thyroid hormone action defects (THADs) are caused by the defective action of thyroid hormones (THs) through their receptors (TRs). TRs variants (TRα1 or TRβ) are associated with several defects, which depend mainly on the tissue-specific expression of the defective-receptor. One of the most striking manifestations is the deregulation of the hypothalamus–pituitary–thyroid axis (HPT); patients with TRα1-mutations show normal thyroid volume, low T4/T3 and...

ea0032p335 | Developmental Endocrinology | ECE2013

The distinctive roles of thyroid hormone receptors in the development of zebrafish tissues

Marelli Federica , Persani Luca

Introduction: As in humans, thyroid hormone (TH) plays an essential role on zebrafish development by acting through the specific nuclear receptors (TRα or TRβ) and activating/suppressing the expression of several target genes. In zebrafish, TRα is preferentially expressed in the heart and CNS while the TRβ is mainly expressed in the retina and inner ear, but the specific role of these receptors in the different target tissues is presently unknown. In this s...

ea0084ps2-09-79 | Thyroid Hormone ACTION | ETA2022

Ectopic expression of human TRA and TRB mutants disentangle the isoform-specific regulation of gene expression during zebrafish development

Marelli Federica , Rurale Giuditta , Persani Luca

Thyroid hormone receptors (TRs) modulate various physiological functions in many organs. The conservation of TRα and TRβ isoforms during evolution of vertebrates suggests different roles for these TRs in thyroid hormone-dependent regulation of gene expression. TRα and TRβ are widely distributed and overlapping in several tissues, and their functional divergence is mainly attributed to their variable tissue expression patterns and intrinsic properties of spe...

ea0049ep1222 | Nuclear receptors and Signal transduction | ECE2017

The human TRα variants affect the specification of haematopoietic stem cells during zebrafish haematopoiesis

Marelli Federica , Rurale Giuditta , Carra Silvia , Persani Luca

Anaemia in RTHα patients correlates with documented abnormal erythropoiesis and reduced haematocrit in TRα-null or mutant mice, but the underlying mechanisms and characterization of the defect remain elusive. In a previous work, we described that the injection of several hTRα variants in zebrafish eggs caused a marked reduction of circulating erythrocytes at later stages of the erythropoiesis. To characterise the involvement of TRα during erythrocyte develo...

ea0041gp171 | Receptors & Signalling | ECE2016

Zebrafish as a new model to study in vivo the functional consequences of human THRA variants

Marelli Federica , Carra Silvia , Rurale Giuditta , Cotelli Franco , Persani Luca

Introduction: Since 2012, different heterozygous mutations in the THRA gene have been described in patients with resistance to thyroid hormone alpha (RTHα). The associating symptoms are reminiscent of untreated congenital hypothyroidism (growth retardation, psycho-neuromotor disorders, delayed bone development and bradycardia) but with raised T3/T4 ratio and normal TSH levels. All genetic abnormalities act in a dominant negative (DN) manner against functional rec...

ea0092op-07-03 | Oral Session 7: Thyroid hormone receptors | ETA2023

Rapid screening of thra variants pathogenicity in the zebrafish model

Marelli Federica , Agostini Maura , Moran Carla , Chatterjee Krishna , Persani Luca

Mutations in THRA, a ligand-inducible transcription factor, cause Resistance to Thyroid Hormone α (RTHα). RTHα manifests with features of hypothyroidism (skeletal dysplasia and growth retardation, neurocognitive impairment, low metabolic rate, reduced intestinal transit) reflecting hormone resistance in TRα-expressing tissues, but associated paradoxically with near-normal circulating TH levels. The lack of clear-cut, abnormal thyroid function tests...

ea0049oc8.2 | Neuroendocrinology | ECE2017

Knocking down/out the prokineticin pathway during zebrafish development results in the GnRH neurons axons misguiding

Bassi Ivan , Marelli Federica , Vezzoli Valeria , Persani Luca , Gothilf Yoav , Bonomi Marco

Studies conducted using knockout mouse model revealed that defects of PROKR2 affect the correct ontogeny of GnRH neurons and, by consequence, neuroendocrine control of reproduction. Nevertheless its exact role during these processes and in the pathogenesis of congenital hypogonadotropic hypogonadism (CHH) remains elusive due to the phenotypic differences observed between mouse and human. Zebrafish (ZF) has emerged in the last ten years as a reliable model organism for studying...

ea0041oc5.5 | Neuroendocrinology | ECE2016

Zebrafish tool for the study of prokineticin receptor 2 (PROKR2) pathway on GNRH3 neuronal development

Bassi Ivan , Marelli Federica , Vezzoli Valeria , Persani Luca , Gothilf Yoav , Bonomi Marco

The G protein-coupled receptor PROKR2 play an important and not fully understood role in GnRH-secreting neurons physiology. Indeed, mutations of PROKR2 in humans are known to cause Congenital Hypogonadotropic Hypogonadism (CHH) although with an important reproductive and olfactory phenotypic heterogeneity. The attempt to mimic PROKR2 human allelic variants in mouse model has so far failed to give insights into the mechanisms involved. The zebrafish (ZF), due to its amenability...

ea0081oc12.3 | Oral Communications 12: Reproductive and Developmental Endocrinology | ECE2022

Defective Notch1/Jag1 signaling impacts GnRH development and contributes to hypogonadotropic hypogonadism

Ludovica Cotellessa , Federica Marelli , Duminuco Paolo , Lucia Bartoloni , Michela Adamo , Pitteloud Nelly , Persani Luca , Bonomi Marco , Giacobini Paolo , Valeria Vezzoli

The precise development of the Gonadotropin Releasing Hormone (GnRH) neurons is essential for the proper function of the hypothalamic-pituitary-gonadal axis, as GnRH is the master regulator of reproductive functions in vertebrates. Mutations in genes involved in the development of GnRH neurons are associated with Congenital Hypogonadotropic Hypogonadism (CHH), a heterogeneous genetic disorder characterized by hypogonadism, lack of puberty onset, and infertility, which is named...

ea0084ps2-09-84 | Thyroid Hormone ACTION | ETA2022

Molecular mechanisms underlying action of triac in resistance to thyroid hormone BETA (RTHβ)

Liao Wenjun , van Geest Ferdy , Marelli Federica , Campi Irene , Moran Carla , Lyons Greta , Agostini Maura , Peeters Robin , Chatterjee Krishna , Persani Luca , Meima Marcel , Edward Visser W.

Background: Resistance to thyroid hormone (TH) beta (RTHβ), caused by mutations in THRB, is characterized by elevated serum (F)T4 accompanied by non-suppressed TSH concentrations. Disease features arise from variable resistance to TH action in tissues expressing Thyroid Hormone Receptor (TR) β (hypothalamus, pituitary, liver) and from thyrotoxic effects in tissues expressing TRα (heart, bone, brain). In symptomatic patients, treatment mainly involves be...