Searchable abstracts of presentations at key conferences in endocrinology

ea0041s17.3 | Genetics and epigenetics of testicular failure | ECE2016

SEMA3A and SEMA3E: from mice to Kallmann syndrome

Cariboni Anna

Gonadotropin releasing hormone neurons are a small group of scattered hypothalamic neuroendocrine cells that control reproductive functions in all mammals and many vertebrates.Despite their position in the adult hypothalamus, during development they originate in the nasal placode and migrate along the vomeronasal nerve to reach the forebrain and attain their final position in the hypothalamus. Failure of GnRH neurons to migrate lead to Kallmann Syndrome,...

ea0051oc4.1 | Oral Communications 4 | BSPED2017

Patients with self-limited delayed puberty harbour mutations in multiple genes controlling GnRH neuronal development

Howard Sasha , Andre Valentina , Guasti Leo , Cabrera Claudia , Barnes Michael , Cariboni Anna , Dunkel Leo

Objectives: Abnormal pubertal timing affects >4% of adolescents and is associated with adverse health outcomes. Up to 80% of variation in the timing of pubertal onset is genetically determined. Self-limited delayed puberty (DP) segregates in an autosomal dominant pattern, but in the majority the neuroendocrine pathophysiology and genetic regulation remain unclear. Mis-regulation of the embryonic migration of GnRH neurons has been implicated in the pathogenesis of DP (Howar...

ea0081ep870 | Reproductive and Developmental Endocrinology | ECE2022

Combined omic analysis revealed autism-linked NLGN3as new candidate gene associated to GnRH neuron development and disease

Oleari Roberto , Lettieri Antonella , J.J. Paganoni Alyssa , Amoruso Federica , Scheiffele Peter , Howard Sasha , Cariboni Anna

During development, gonadotropin releasing hormone (GnRH) neurons are born in the nasal placode and migrate to the hypothalamus, where they position to regulate sexual reproduction by the pulsatile release of GnRH. Defective GnRH neuron development or action may lead to GnRH deficiency (GD) which is characterized by absent or delayed puberty (1). GD can also be present as a trait shared by several complex neurodevelopmental disorders (NDDs), such as cerebellar ataxia, developm...

ea0014oc7.2 | Reproductive endocrinology I | ECE2007

Neuropilin-2 and its ligands are involved in the migration of GnRH-secreting neurons

Cariboni Anna , Rakic Sonja , Hickok Jason , Andrews William , Tischkau Shelley , Maggi Roberto , Parnavelas John

Reproduction in mammals is centrally regulated by neuroendocrine neurons scattered in the hypothalamus and secreting the decapeptide GnRH (gonadotropin releasing hormone). During development, GnRH-secreting neurons originate in the olfactory placode – at least in rodents – and migrate along olfactory nerves (the vomeronasal and the terminalis) to gain access to the forebrain and reach their final destinations in the hypothalamus. Defects in the migration of these neu...

ea0014oc11.2 | Reproductive endocrinology II | ECE2007

Leukemia inhibitory factor promotes the chemomigration of immature GnRH neurons

Dozio Elena , Ruscica Massimiliano , Cariboni Anna , Watanobe Hajime , Motta Marcella , Maggi Roberto , Magni Paolo

Leukemia inhibitory factor (LIF), a pleiotropic cytokine of the interleukine-6 superfamily, is involved in several functions including the control of reproduction at the embrionic-endometrial interface and the regulation of energy homeostasis. LIF activates a cell-surface receptor complex (LIF-Rs) composed of one ligand-specific low affinity LIF receptor β (LIFRβ) subunit and the gp130 subunit. Since little is known about the involvement of LIF in the modulation of t...

ea0034p158 | Growth and development | SFEBES2014

A novel gene affecting the timing of puberty

Howard Sasha , Guasti Leo , Storr Helen , Metherell Lou , Cariboni Anna , Barnes Michael , Cabrera Claudia , Wehkalampi Karoliina , Dunkel Leo

Background: Disturbances of pubertal timing affect >4% of the population and are associated with adverse health outcomes. Studies estimate 60–80% of variation in pubertal onset is genetically determined, but few genetic factors are known. We hypothesise that causal variants will be low-frequency, intermediate-impact variants and will be enriched in populations at the extremes of normal pubertal timing. Families with constitutional delay in growth and puberty (CDGP) ha...

ea0066oc4.3 | Oral Communications 4 | BSPED2019

Defects in LGR4 Wnt-β-catenin signalling impair GnRH network development, leading to delayed puberty

Mancini Alessandra , Howard Sasha R , Cabrera Claudia P , Barnes Michael R , David Alessia , Wehkalampi Karoliina , Vassert Gilbert , Cariboni Anna , Garcia Maria Isabelle , Guasti Leonardo , Dunkel Leo

Background: The initiation of puberty is heralded by increasing gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus. During embryonic life the GnRH neuroendocrine network develops thanks to a coordinated migration of neurons from the nasal placode to the forebrain. Our group has previously demonstrated that dysregulation in GnRH neuronal migration leads to delayed pubertal onset. Late puberty affects up to 2% of the population and is associated with adverse h...

ea0063gp69 | Reproductive Axis | ECE2019

Male patients with hypogonadism have an impaired lipoprotein function

Cangiano Biagio , Adorni Maria Pia , Zimetti Francesca , Vezzoli Valeria , Bernini Franco , Caruso Donatella , Corsini Alberto , Sirtori Cesare R. , Cariboni Anna , Ruscica Massimiliano , Bonomi Marco

Background: Male hypogonadism is known to be associated with an increased incidence of cardiovascular (CV) events, although the underlying biochemical mechanisms are so far not fully understood. The clinical condition characterized by low levels of testosterone offers a unique model to unravel the possible role of lipoprotein-associated abnormalities in CV risk. In particular, the assessment of the functional capacities of high-density lipoproteins (HDL) may provide novel insi...

ea0016p398 | Neuroendocrinology | ECE2008

Genetic and clinical analyses in an Italian series of idiopathic hypogonadotropic hypogonadism

Bonomi Marco , Antonica Francesco , Cariboni Anna , Busnelli Marta , Pia Anna , Borretta Giorgio , Beck-Peccoz Paolo , Krausz Csilla , Maggi Roberto , Persani Luca

Idiopathic hypogonadotropic hypogonadism (IHH) is a rare and heterogeneous disease due to defects of GnRH secretion or action. IHH could be associated or not with anosmia respectively identifying the Kallmann’s syndrome (KS) or the normosmic IHH (nIHH). So far numerous causative genetic defects have been described, but very recent molecular genetic studies and animal models have opened novel perspectives. We are studying a series of 16 KS (14M,2F) and 18 nIHH (14M,4F). Al...

ea0039oc5.1 | Oral Communications 5 | BSPED2015

Mutations in IGSF10 cause self-limited delayed puberty

Howard Sasha , Guasti Leonardo , Ruiz-Babot Gerard , Mancini Alessandra , David Alessia , Storr Helen , Metherell Louise , Cabrera Claudia , Warren Helen , Barnes Michael , Wehkalampi Karoliina , Gothilf Yoav , Andre Valentina , Cariboni Anna , Dunkel Leo

Background: Abnormal pubertal timing affects over 4% of adolescents and is associated with adverse health and psychosocial outcomes. Previous studies estimate that 60–80% of variation in the timing of pubertal onset is genetically determined. However, despite this strong heritability, little is known about the genetic control of human puberty. Self-limited delayed puberty (DP) segregates in an autosomal dominant pattern, but in the majority of patients the neuroendocrine ...