Short Stature in Childhood - Challenges and Choices.
ABSTRACT This article reviews evaluation of short stature in childhood and options for management of idiopathic cases (e.g., familial short stature or constitutional delay of growth and puberty), including observation and reassurance, growth hormone treatment, and low-dose oral oxandrolone in boys.
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ABSTRACT: Growth hormone (GH) exerts a diverse array of physiological actions that includes prominent roles in growth and metabolism, with a major contribution via stimulating insulin-like growth factor-1 (IGF-1) synthesis. GH achieves its effects by influencing gene expression profiles, and Igf1 is a key transcriptional target of GH signaling in liver and other tissues. This review examines the mechanisms of GH-mediated gene regulation that begin with signal transduction pathways activated downstream of the GH receptor and continue with chromatin events at target genes, and additionally encompasses the topics of negative regulation and crosstalk with other cellular inputs. The transcription factor Stat5b is regarded as the major signaling pathway by which GH achieves its physiological effects, including in stimulating Igf1 gene transcription in liver. Recent studies exploring the mechanisms of how activated Stat5b accomplishes this are highlighted, which begin to characterize epigenetic features at regulatory domains of the Igf1 locus. Further research in this field offers promise to better understand the GH-IGF-1 axis in normal physiology and disease and identify strategies to manipulate the axis to improve human health.Molecular Endocrinology 05/2014; 28(7):me20141099. · 4.20 Impact Factor