Endocrine Abstracts

The prohormone T4 represents the majority of circulating thyroid hormones, whereas 80% of the active hormone T3 is derived from T4 by the actions of the type 1 and type 2 deiodinase enzymes (D1 and D2). Local generation of T3 by D2 regulates ligand supply to the nuclear T3-receptor in pituitary, brown adipose tissue and brain, and this enzyme is also expressed in bone. Hypothyroidism in children causes delayed bone age and growth retardation, whereas thyrotoxicosis in adults c...

Hypothyroidism causes delayed ossification and growth retardation. T3 stimulates hypertrophic chondrocyte differentiation whereas unliganded T3 receptors (TRs) repress gene expression and maintain cell proliferation in the absence of hormone. During development the type 3 deiodinase enzyme (D3) inactivates thyroid hormones and prevents T3-access to the fetus. At birth diminishing D3 activity and increasing T3 availability triggers the onset of cell differentiation and correlat...

Background: EIF2S3 (NM_001415; Xp22.11) mutations have previously been reported in a single pedigree with microcephaly and developmental delay. The gene encodes the eukaryotic translation initiation factor 2 subunit 3 (eIF2γ), the largest of three EIF2 subunits. EIF2 is a heterotrimeric GTP-binding protein, which initiates protein synthesis. It forms a ternary complex, mediating recruitment of initiator methionyl-tRNA to the 40S ribosomal subunit to scan the mRNA...

Keith Parker, University of Texas Southwestern Medical Center, Dallas, TX, USA AbstractThe son of two clinician-scientists, Keith Parker attended Williams College, and then received his M.D./Ph.D. degrees from Washington University School of Medicine in 1981. His graduate work with Donald Shreffler focused on structure-function relationships of the complement component, C4....

Context: Severe or ‘classical’ growth hormone insensitivity (GHI) is characterised by extreme short stature, dysmorphism and metabolic anomalies. It is caused by homozygous or compound heterozygous mutations of the Growth Hormone Receptor gene (GHR). Genetic analysis traditionally focuses on the exonic regions of gene(s). The non-coding regions of the genome may harbour numerous disease-causing mutations that are not well recognised or understood.<p clas...

Introduction: Primary aldosteronism (PA) is the most common surgically curable cause for endocrine hypertension. Patients with unilateral aldosterone-producing adenoma undergo adrenalectomy (ADX). Clinical and biochemical outcome is assessed 6-12 months after ADX according to PASO consensus. To reduce unnecessary follow-up visits and change in medication for diagnostic purposes for potentially cured patients after ADX, a prediction tool is needed. Previous research had shown g...

Introduction: Sphingosine-1-phosphate lyase (SGPL1) catalyses the final step in sphingolipid metabolism, irreversibly degrading the lipid signalling molecule sphingosine-1-phosphate (S1P). The relative abundance of S1P compared to its precursors sphingosine and ceramide finely tunes signal transduction for a wide range of cellular pathways including proliferation, apoptosis, migration and calcium handling. Loss-of-function mutations in SGPL1 cause a spectrum of disorders, incl...

T3 is an important regulator of skeletal development and adult bone maintenance. Thyroid hormone action requires efficient transport of T4 and T3 into target cells. We hypothesized that monocarboxylate transporter-8, encoded by Mct8 on the X-chromosome, is an essential thyroid hormone transporter in bone. To test this hypothesis, we determined the juvenile and adult skeletal phenotypes of male Mct8 knockout mice (Mct8KO) and Mct8D1D2KO compo...

T3 is an important regulator of skeletal development and adult bone maintenance. Thyroid hormone action requires efficient transport of T4 and T3 into target cells. We hypothesized that monocarboxylate transporter-8, encoded by Mct8 on the X-chromosome, is an essential thyroid hormone transporter in bone. To test this hypothesis, we determined the juvenile and adult skeletal phenotypes of male Mct8 knockout mice (Mct8KO) and Mct8D1D2KO compo...

Background: Obesity exacerbates a number of chronic inflammatory diseases including asthma, with increasing adiposity observed to worsen asthma severity and disease control. This exacerbation may arise as gut-derived bacterial fragments (endotoxin) and associated markers of endotoxin (lipopolysaccharide binding protein (LPB)), enter the circulation through a damaged gut barrier, provoking systemic inflammation. This study investigated the role of body weight on gut permeabilit...