Effects of Growth Hormone and IGF

Effects of Growth Hormone (GH)

• GH has direct effects on various tissues and organs
• Increases amino acid (AA) uptake
• Increases protein synthesis
• Decreases protein breakdown
• Influences glucose entry into cells
• Directly alters lipid metabolism
• Decreases glucose uptake
• Increases lipolysis (fat breakdown)
• Leads to increased free fatty acids (FFA)
• Results in insulin resistance
• Causes hyperglycemia (high blood glucose)
• Increases insulin secretion
• Stimulates IGF-1 production
• Stimulates gluconeogenesis
• Stimulates glycogenolysis
• Impacts protein synthesis
• Affects AA uptake

IGF and Insulin Receptors

• IGF-1, Insulin, and IGF-1 receptors share structural similarities
• Hybrid receptors exist between insulin and the IGF-1 receptor
• Metabolic effects and mitogenic effects are both influenced by these receptors

IGF Family: Receptors and Binding Proteins

• IGF binding proteins (IGFBPs) are crucial for IGF function
• IGFBPs bind circulating IGFs with high affinity
• They act as carriers for IGFs in the bloodstream
• Prolong the half-life of IGFs
• Regulate IGF access to its receptors
• Function through receptor interaction, regardless of the presence of IGFs

Insulin-like Growth Factor Binding Proteins (IGFBPs)

• IGFBPs bind circulating IGFs with high affinity
• Act as carriers for IGFs
• Prolong IGF half-life
• Regulate IGF access to receptors
• Function independent of IGFs

IGFBPs—Modify IGF Activity

• IGFBP-3 is the most prevalent form of IGFBP
• Main carrier of IGF in circulation
• Promotes somatic growth related to IGF
• Associated with growth stimulation
• IGFBP-1 is typically present in small amounts
• Associated with growth inhibition

Binding Proteins Regulate Free IGF Availability

• Binding proteins influence IGF availability to receptors
• Decidual IGFBP-1 and placental IGFs have critical roles during implantation
• High levels of placental IGF with low levels of decidual IGFBP-1 lead to abnormal invasion
• Controlled invasion leads to a normal placenta
• Low levels of placental IGF with high levels of decidual IGFBP-1 lead to shallow implantation, abortion, and placental dysfunction
• High levels of both are linked to tubal pregnancies and abnormal placental structures (increta/percreta)

Insulin-like Growth Factors - Somatomedins

• IGF-1 and IGF-2 are somatomedins
• IGF-1 (somatomedin-C):
  • 70 amino acids
  • 50% homology with insulin
  • Stimuli for secretion: GH, nutritional status
• IGF-2:
  • 67 amino acids
  • 70% homology with insulin
• Stimuli for secretion: Nutritional status, GH

Bone Cell-Specific Effects of IGFs

• IGFs promote bone cell proliferation and maturation
• Regulate the stem cells pool and lineage commitment
• Affect mesenchymal and hematopoietic stem cells
• Influence osteoclast activity and fusion-induced multinucleation
• Impact osteocyte network integrity
• Promote differentiation and mineralization of osteoblasts
• Affect growth plate zones

Other Effects of Growth Hormone

• Adipose tissue: Increased lipogenesis
• Extra skeletal tissue: Cell growth proliferation and protein synthesis
• Blood glucose: Overall increase in plasma glucose, insulin resistance, decreased glucose uptake, and pituitary diabetes

GH Hormone Deficiency: Pre-Puberty

• Most common pituitary hormone deficiency in children
• Isolated or accompanied by deficiency in other pituitary hormones
• Panhypopituitarism: Rare condition – reduced production of all pituitary hormones
• GH deficiency leads to slow growth and short stature

Growth Hormone Deficiency: Pre-puberty Manifestations

• Growth failure: Height below 3rd percentile
• Slow growth velocity: <6 cm/year before age 4, <5 cm/year from age 4 to 8, <4 cm/year before puberty
• Short stature
• Normal proportionality
• Skeletal maturation delayed by more than 2 years
• May have delayed tooth development
• Delayed or absent pubertal development
• Relative obesity

GH Pre-Puberty Deficiency: Clinical Assessment

• Height and weight data are recorded on a growth chart
• Imaging studies: X-rays (bone age), MRI (pituitary gland and hypothalamus)
• Hormone and binding protein measurements
• GH stimulation tests (arginine)

Growth Deficiencies Unrelated to GH Deficiency

• Laron syndrome: GH insensitivity or primary IGF-1 deficiency
• Rare genetic disease (autosomal recessive manner)
• Genetic mutations in the growth hormone receptor gene
• Defect in GH and IGF-1 signaling pathway
• Genetic IGF deficiency
• Nutritional neglect

Undersecretion Post Puberty

• Lack of GH leads to altered metabolism, increased adiposity, excessive tiredness, increased cardiovascular disease (CVD), anxiety, depression, and reduced quality of life

Over-Secretion of GH

• Age-dependent Gigantism (prepuberty)
• Post-puberty Acromegaly

Acromegaly (Over-Secretion)

• Rare condition, develops between ages 30-50
• Mostly due to benign pituitary tumors (>99% of cases)
• Symptoms include thickened skin, coarse facial features, enlarged hands, feet, lips, nose, and tongue; jaw protrusion; thickened ribs, barrel chest, organ enlargement; cardiovascular (CVS) disease; upper airway obstructions, sleep apnea; carbohydrate intolerance, pituitary diabetes, and general tiredness

Fetal Growth

• Fetal growth is controlled by various factors, including growth hormones.

This quiz explores the complex effects of Growth Hormone (GH) on various tissues and its relationship with Insulin-like Growth Factor (IGF). Learn about GH's impact on metabolism, protein synthesis, and its interactions with Insulin receptors. Test your knowledge on the roles of IGF and its binding proteins in metabolic functions.