Growth Hormone/Insulin like growth factor - I Axis Flashcards
What is growth hormone essential for?
Linear growth in postnatal life
Metabolic actions
What are the anabolic effects of GH mediated by?
IGF-I that is produced in the liver
Which neuroendocrine cells are involved in the regulation of GH secretion?
Arcuate, dorso and ventromedial nuclei of hypothalamus
What inhibits GH secretion?
NEFAs
What 2 things can increase GH secretion?
Low blood glucose (hypoglycemia)
Vigorous excercise
What is somatopause?
Normal age related decline in GH (and IGF-I) of ~50%
What are 2 patterns of regulation of GH secretion?
Pulsatile secretion - 3-4h intervals
Circadian rhythm - peak secretion at onset of REM4
Where does bone elongation occur?
At epiphyseal growth plate
What is the differentiation and proliferation of chondrocytes controlled by?
GH and IGF-I
What causes the closure of the growth plate?
Mineralisation
What pathway does GH receptor signaling use?
JAK-STAT pathway
What are the major metabolic actions of GH?
Increases plasma glucose levels -> inhibits glucose uptake in adipose tissue and skeletal muscle by reducing insulin sensitivity
Increases lipolysis in adipose tissue -> increases circulating FA levels
Shifts energy metabolism to FA oxidation
What are the major metabolic actions of GH?
Increases plasma glucose levels -> inhibits glucose uptake in adipose tissue and skeletal muscle by reducing insulin sensitivity
Increases lipolysis in adipose tissue -> increases circulating FA levels
Shifts energy metabolism to FA oxidation
What 2 ways is IGF-I produced?
Circulating = liver (GH dependent)
Produced in extrahepatic tissues (GH independent)
What are 4 ways of IGF-I regulation?
GH
Nutritional status
Insulin
Somatopause
What is IGF-I’s anabolic action?
GH dependent and independent actions to promote fetal and postnatal growth
What are 4 metabolic actions of IGF-I?
Increase glucose uptake/utilization in skeletal muscle
Increase protein synthesis in skeletal muscle
Increase insulin sensitivity
Decrease GH secretion
What is congenital GH deficiency?
Decreased GH and IGF-I - growth failure in early childhood. Primary manifestations often metabolic
What are 3 causes of congenital GH deficiency?
Birth trauma
Midline defect syndrome
Mutations of transcription factors controlling pituitary differentiation
How can congenital GH deficiency be treated?
GH replacement therapy
What four ways can acquired GH deficiency in childhood result from?
Trauma
Infections
Cranial irradiation
Systemic diseases
What are 5 symptoms of Gh deficiency in children?
Short stature
low growth velocity for age/pubertal stage
Increased fat around waist
Delayed tooth development
Delayed onset of puberty
What is Laron Dwarfism?
Autosomal recessive disorder -> GH receptor deficiency
Increased GH and decreased IGF-I
What are 4 characteristics of Laron Dwarfism?
Short stature
Hypoglycemia
Poor muscle development
Obesity
