The AgRP and GH/IGF-1 Axis in Children

Recent data support the existence of a GH-Agouti-related peptide (AgRP) axis. The neuropeptide AgRP promotes food intake and has important effects on energy homeostasis. Recent evidence suggest that GH stimulates AgRP and AgRP may mediate some of GH's important nutritional and metabolic effects. main goals of this project are to characterize, for the first time, plasma levels of AgRP in children and to determine how these relate to GH and IGF-1 levels, age, body composition, clinical and other endocrine parameters. To accomplish this, we will conduct two studies, one being a cross-sectional study that will measure AgRP levels in 140 healthy children ages 5-17 and the second being a prospective study that will measure the change in plasma AgRP levels in response to GH treatment in 16 children who receive this as part of their clinical care for GH deficiency or short stature.

Healthy childrenInclusion Criteria:Ambulatory male and female children aged 5-17 yearsNormal weight at birthHeight between the 3rd and 99th percentiles of the mean as per the CDC growth percentiles.Exclusion Criteria:Genetic defects, chronic illnesses.Current prescription medication useUse of glucocorticoids, thyroid hormone or medications that may affect the GH-IGF-1 axis within 6 months of study entry.Children with GH deficiency:Inclusion Criteria:Ambulatory male and female children aged 5-9 years who are prepubertalNormal weight at birthGrowth failurePeak GH response to 2 GH stimulation tests < 10 ng/mlNormal renal and liver functionExclusion criteria:Multiple pituitary hormone deficiencies,GH deficiency or poor growth associated with any acute or chronic medical condition such as renal disease or Turner's syndrome.History of diabetes or malignancyUse of glucocorticoids or medications known to affect the GH-IGF-1 axis within 6 months of study entry.Children with idiopathic Short Stature:Inclusion Criteria:Ambulatory male and female children aged 5-9 years who are prepubertalNormal weight at birthHeight >2.25 SD below mean for agePeak GH response to 2 stimulation tests >10 ng/ml or normal IGF-1 and IGFBP-3 levelsNo prior supplemental growth hormone exposureNormal renal and liver functionExclusion criteria:Poor growth associated with any acute or chronic medical condition such as renal disease or Turner's syndrome.History of diabetes or malignancyUse of glucocorticoids or medications known to affect the GH-IGF-1 axis within 6 months of study entry.