Effects of Growth Hormone PDF

Effects of Growth Hormone  Direct Effects of GH ↓ Lipogenesis ↑ Protein Synthesis ↑ AA uptake Increases...

Effects of Growth Hormone  Direct Effects of GH ↓ Lipogenesis ↑ Protein Synthesis ↑ AA uptake Increases AA Uptake Increases Protein Synthesis Decreases Protein Breakdown Decreases Glucose Entry IGF and Insulin Receptors  IGF Family: Receptors and Binding Proteins  Insulin-like Growth Factor Binding Proteins (IGFBPs) IGFBPs bind circulating IGF with high affinity & specificity Functions Act as carriers of IGF in plasma Prolong the half-life of IGF in circulation Regulate IGF access to receptor Function through receptor interaction independent of IGFs  IGFBPs—Modify IGF activity IGFBP-3 Most abundant form of IGFBP Main carrier of IGF in circulation Promotes IGF mediated somatic growth High IGFBP-3 associated w/ growth stimulation IGFBP-1 Typically present in small amounts High IGFBP-1 associated with growth inhibition Binding Proteins Regulate Free IGF availability to receptors Insulin Like Growth Factors - Somatomedins Insulin-like growth factor 1 (IGF-1) (somatomedin C) 70 a.a.; 50% homology with insulin Stimuli for secretion GH, nutritional status to a lesser extent Insulin-like growth factor 2 (IGF-2) 67 a.a.; 70% homology with insulin Stimuli for secretion Nutritional status, GH to a lesser extent University ofGalway.i e  Other Effects of Growth Hormone Adipose Tissue Increased Lipogenesis Extra Skeletal Tissue Cell Growth Proliferation Protein Synthesis Effects on blood glucose – Diabetogenic effect Overall, increases plasma glucose Insulin resistance and decreases glucose uptake Pituitary Diabetes University ofGalway.i e  GH Hormone Deficiency: Pre-Puberty Most common pituitary hormone deficiency in children Isolated or accompanied by deficiency of other pituitary hormones Panhypopituitarism Rare condition – reduced production and of all pituitary hormones GH deficiency typically results in slow growth and short stature University ofGalway.i e  Growth hormone Deficiency: Pre-puberty Typically manifests as growth failure - Height below the 3rd percentile Growth velocity is < 6 cm/year before age 4 years < 5 cm/year from age 4 to 8 years < 4 cm/year before puberty Small stature Normal proportionality between upper and lower body segments University Skeletal maturation is > 2 years behind chronologic ofGalway.i e age.  Growth hormone Deficiency: Pre-puberty May also be present, depending on the underlying defect Delay in tooth development. Delayed or absent pubertal development Weight gain may be out of proportion to growth - relative obesity. Hypoglycemia Manifestations of other endocrine deficiencies University ofGalway.i e  GH Pre-Puberty Deficiency: Clinical Assessment Height and weight data recorded on a growth chart Imaging studies X- Ray determines Bone age (left hand by convention) GH deficiency - skeletal maturation delayed to same extent as height MRI - Evaluating the pituitary gland and hypothalamus Calcifications, tumors, and structural anomalies University ofGalway.i Hormones and Binding Protein Measurements e Hormone stimulation tests - Arginine  Growth Deficiencies Unrelated to GH Deficiency Laron Syndrome Laron syndrome (GH insensitivity) or primary IGF-1 deficiency Rare genetic disease inherited in an autosomal recessive manner Genetic mutations of the growth hormone receptor gene Defect in the signaling pathway GH and IGF1 Genetic IGF Deficiency University ofGalway.i e Nutritional Neglect Undersecretion Post Puberty Lack of GH leads to: – Altered Metabolism – Increased Adiposity – Excessive tiredness – Increased CV Disease – Anxiety – Depression – Reduced “quality of life” University ofGalway.i e  Over-Secretion of GH University ofGalw Age Dependent Gigantism Prepuberty ay.i e  Over-Secretion of GH Post Puberty Acromegaly U niversity ofGalway.i e  Acromegaly Rare condition –Develops between ages 30-50 Causes >99% of cases due to benign Tumor of Pituitary Symptoms: Thickening of Skin, Coarse facial features Enlarged hands, feet, Lips, Nose Tongue Jaw protrusion Thickened Ribs - Creating Barrel Chest Organ enlargement – CVS Disease Upper Airway Obstructions Leading to Sleep Apnea Carbohydrate Intolerance - Pituitary Diabetes General Tiredness University ofGalway.i e  Fetal Growth What controls it? 54cm Universi ofGalwa 100µm ty y.i e