Growth Hormone and IGF Overview

Growth Hormone Effects

• Growth hormone (GH) has direct and indirect effects on the body
• Direct effects include increasing amino acid uptake, protein synthesis, and decreasing protein breakdown
• GH also impacts glucose uptake, leading to increased blood glucose levels (hyperglycemia).
• This is because GH reduces glucose uptake and increases glucose production, leading to insulin resistance.

IGF and Insulin Receptors

• IGF-1 and insulin receptors share a structural similarity
• IGF-1 receptors have an important metabolic effect and a mitogenic effect.
• Insulin receptors have a major metabolic effect.
• Important for growth as they are both involved in cell growth, differentiation and functions.

IGF Family

• IGF binding proteins (IGFBPs) bind to insulin-like growth factor (IGF) in the blood
• These proteins act as carriers, increasing IGF lifetime in the circulation
• IGFBPs regulate IGF-receptor access, having independent functionality to IGF itself
• Different IGFBPs have different effects (e.g., IGFBP-3 promotes growth, IGFBP-1 inhibits it), impacting overall growth and development.

IGFBP- Modifying IGF activity

• IGFBP-3 is the most common form of IGFBP
• IGFBP-3 is a primary carrier of IGF in the circulation and promotes somatic growth. High IGFBP-3 is associated with growth stimulation.
• IGFBP-1 is typically present in smaller amounts and is associated with growth inhibition.

Binding Proteins and Receptors

• Binding proteins of IGF regulate IGF availability to receptors in the body
• Different levels of binding proteins lead to different states of IGF receptor activity. E.g. increased placental IGF, decreased decidual IGFBP-1 levels result in unlimited invasion.

Insulin-like Growth Factors - Somatomedins

• IGF-1 (somatomedin C) is 70 amino acids and has a 50% homology with insulin
• IGF-2 is 67 amino acids with 70% insulin homology
• Stimuli for secretion include GH and nutritional status.

Bone Cell-Specific Effects of IGFs

• IGFs promote proliferation, maturation, and differentiation of bone cells involved in bone development.
• IGFs regulate stem cell pools contributing to bone lineage commitment.
• IGFs influence osteoclast activity, fusion, and multinucleation.
• They interact with the osteocyte network maintaining integrity.

Other Effects of Growth Hormone

• Adipose tissue – increased lipogenesis.
• Extra skeletal tissue – cells growth proliferation and protein synthesis
• Effects on blood glucose (diabetogenic effect): Overall increase in plasma glucose, insulin resistance, reductions in glucose uptake, and pituitary diabetes.

GH Hormone Deficiency: Pre-Puberty

• Most frequent pituitary hormone deficiency in childhood
• Can be isolated or accompanied by deficiency in other pituitary hormones.
• Panhypopituitarism (rare) is a condition involving a reduced production of all pituitary hormones.
• GH deficiency leads to slow growth and short stature.

Growth Hormone Deficiency: Pre-puberty (Clinical manifestations)

• Growth failure, with height below the 3rd percentile
• Typically characterized by slow growth velocity (less than 6 cm/year before age 4, less than 5 cm/year from age 4 to 8, and less than 4 cm/year before puberty).
• Small stature, and relatively normal body proportions.
• Delayed skeletal maturation, usually 2 years or more behind the child's chronological age.
• Delays in tooth development, pubertal development, relative obesity.
• Possible hypoglycemia or manifestations of other endocrine issues.

GH Pre-Puberty Deficiency Assessment and Diagnosis

• Comprehensive data collection: height and weight recorded on a growth chart
• Medical imaging, including X-rays (bone age), and MRI (for pituitary gland & hypothalamus evaluation) along with structural anomalies
• Hormone and binding protein measurements, along with GH stimulation tests (e.g., arginine).

Growth Deficiencies Unrelated to GH Deficiency

• Laron syndrome (GH insensitivity or primary IGF-1 deficiency): rare genetic disease, inherited in autosomal recessive pattern. Genetic mutations of growth hormone receptor gene impacting the GH/IGF-1 signaling pathway
• Nutritional Neglect
• Genetic IGF Deficiency

Undersecretion Post-Puberty

• Lack of GH post-puberty: altered metabolism, increased adiposity, increased tiredness.
• Increased cardiovascular disease risk.
• Anxiety and depression
• Reduced "quality of life"

Over-Secretion of GH

• Age-dependent gigantism (pre-puberty): Characterized by excessive growth during childhood.
• Post-puberty: Acromegaly: A condition with an overproduction of GH in adulthood. Slow bone and soft tissue growth, leading to characteristic enlarged bones, and soft tissue structures in the face, hands, and feet. Thickened skin and a broader face and larger hands and feet.

Acromegaly Symptoms

• Thickened skin, coarse facial features, enlarged hands, feet, and lips, nose and tongue
• Jaw protrusion, ribs thickening leading to barrel chest, organ enlargement (CV disease risk), upper airway obstructions ("sleep apnea")
• Carbohydrate intolerance, pituitary diabetes and general tiredness.

Fetal Growth

• Factors that control fetal growth are complex and not fully understood

Explore the effects of growth hormone on the body, including its role in protein synthesis and glucose regulation. Learn about the similarities between IGF-1 and insulin receptors, as well as the importance of IGF binding proteins in metabolic processes. This quiz will deepen your understanding of hormonal interactions and their physiological impacts.