Growth Hormone/Insulin like growth factor - I Axis

Question 1

What is growth hormone essential for?

Answer 1

Linear growth in postnatal life
Metabolic actions

Question 2

What are the anabolic effects of GH mediated by?

Answer 2

IGF-I that is produced in the liver

Question 3

Which neuroendocrine cells are involved in the regulation of GH secretion?

Answer 3

Arcuate, dorso and ventromedial nuclei of hypothalamus

Question 4

What inhibits GH secretion?

Answer 4

NEFAs

Question 5

What 2 things can increase GH secretion?

Answer 5

Low blood glucose (hypoglycemia)
Vigorous excercise

Question 6

What is somatopause?

Answer 6

Normal age related decline in GH (and IGF-I) of ~50%

Question 7

What are 2 patterns of regulation of GH secretion?

Answer 7

Pulsatile secretion - 3-4h intervals
Circadian rhythm - peak secretion at onset of REM4

Question 8

Where does bone elongation occur?

Answer 8

At epiphyseal growth plate

Question 9

What is the differentiation and proliferation of chondrocytes controlled by?

Answer 9

GH and IGF-I

Question 10

What causes the closure of the growth plate?

Answer 10

Mineralisation

Question 11

What pathway does GH receptor signaling use?

Answer 11

JAK-STAT pathway

Question 12

What are the major metabolic actions of GH?

Answer 12

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

Question 12

What are the major metabolic actions of GH?

Answer 12

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

Question 13

What 2 ways is IGF-I produced?

Answer 13

Circulating = liver (GH dependent)
Produced in extrahepatic tissues (GH independent)

Question 14

What are 4 ways of IGF-I regulation?

Answer 14

GH
Nutritional status
Insulin
Somatopause

Question 15

What is IGF-I’s anabolic action?

Answer 15

GH dependent and independent actions to promote fetal and postnatal growth

Question 16

What are 4 metabolic actions of IGF-I?

Answer 16

Increase glucose uptake/utilization in skeletal muscle
Increase protein synthesis in skeletal muscle
Increase insulin sensitivity
Decrease GH secretion

Question 17

What is congenital GH deficiency?

Answer 17

Decreased GH and IGF-I - growth failure in early childhood. Primary manifestations often metabolic

Question 18

What are 3 causes of congenital GH deficiency?

Answer 18

Birth trauma
Midline defect syndrome
Mutations of transcription factors controlling pituitary differentiation

Question 19

How can congenital GH deficiency be treated?

Answer 19

GH replacement therapy

Question 20

What four ways can acquired GH deficiency in childhood result from?

Answer 20

Trauma
Infections
Cranial irradiation
Systemic diseases

Question 21

What are 5 symptoms of Gh deficiency in children?

Answer 21

Short stature
low growth velocity for age/pubertal stage
Increased fat around waist
Delayed tooth development
Delayed onset of puberty

Question 22

What is Laron Dwarfism?

Answer 22

Autosomal recessive disorder -> GH receptor deficiency
Increased GH and decreased IGF-I

Question 23

What are 4 characteristics of Laron Dwarfism?

Answer 23

Short stature
Hypoglycemia
Poor muscle development
Obesity

Question 24

How is Laron Dwarfism treated?

Answer 24

IGF-I

Question 25

What are the 3 main causes of adult onset GH deficiency (AGHD)?

Answer 25

Pituitary tumors
Head trauma
Vascular abnormalities

Question 26

What are 4 features of AGHD?

Answer 26

Metabolic abnormalities
Altered body composition
Osteoporosis
Psychological disorders

Question 27

What are 2 types of acromeagaly?

Answer 27

Congenital (pre-puberty) - gigantism
Acquired (adult onset) - bone thickening and metabolic abnormalities

Question 28

What is the main cause of acromegaly?

Answer 28

Functioning pituitary adenoma of somatotroph origin