Growth Hormone Physiology
What is Dwarfism?
- GH deficiency during childhood - In adults = hypothyroidism, ↓ glucocorticoids, ↓ gonadotropic hormones
Where do IGFs have a similar job to insulin?
Adipose and liver → Freeing glucose and Fatty acids
What is the primary site of GHBP?
Adipose tissue
What does IGF receptor type 2 bind?
Binds IGF 2 with more affinity than 1 → Clearance receptor for IGF 2 → mostly inactive
What is the major paracrine role of IGFBP-5?
Bone matrix development
What hormone increases GH before a meal?
Ghrelin
What controls Growth Hormone?
Growth Hormone Releasing Hormone (GHRH)= stimulation Somatostatin (SRIF) = Inhibition → NOT under tonic control
What conditions inhibit GH release?
Hyperglycemia, ↑ insulin, ↑ free fatty acids
What conditions stimulate GH release?
Hypoglycemia, ↑ amino acids (starvation), stress
Where is IGF-2 mostly located?
Liver
Where is IGF -1 located?
Liver, brain, muscle and bone - IT IS ESSENTIAL
What type of feedback do IGFs exert on SRIF and GHRH?
Long feedback loop on hypothalamus
What is GH responsible for in the adult?
Maintaining body mass and facilitate compensatory growth
Where do IGFs have a similar job to Growth hormone?
Muscle → Stimulating protein synthesis
What is the primary function of growth hormone?
Regulating growth though IGFs
What does IGF-2 regulate?
Somatomedin A Predominant in adults, not essential but deficiency does show abnormal growth.
What does IGF-1 regulate?
Somatomedin C 1. Fetal development and major organs
What is a unique aspect about GHBP?
They are active endocrine/paracrine molecules and although there are 6 types, they are all highly homologous
What is the major paracrine role of IGFBP-4?
Tissue specific
What is the major paracrine role of IGFBP-1?
amniotic fluid development
What is the major paracrine role of IGFBP-2 and IGFBP-6?
cerebrospinal fluid development
What does IGF receptor type 1 bind?
→ Binds IGF 1 and 2 with high affinity → Most active
What is the major endocrine role of IGFBP-3?
→ Major carrier in circulation → Stimulates endocrine function
Which manner is GH released?
→ Surges during night time (specially deep-sleep) → Episodic releases during exercise and fasting (promoting mobilization of fuel stores)
What is Acromegaly?
Excessive GH in adults (epiphysis closed)
What is Gigantism?
Excessive GH in children (epiphysis still open)
What are the steps in GHBP synthesis?
1. GH receptor gene is activated & protein is translated 2. GH receptor protein migrates to cell membrane and begins to integrate 3. 50% of GH receptors undergo post-translational processing and extracellular domain is spliced, intracellular domain remains intact - Intracellular domain IS the GH receptor - Extracellular becomes the GH binding protein 4. Extracellular domain circulates in serum and binds GH - referred to as "soluble GH receptor"
What are the actions of GH?
1. ↑ lipolysis in adipose 2. ↓ glucose uptake in muscle 3. ↑ hepatic glucogenesis
What is the major paracrine role of IGFBP-3?
Follicular fluid development
What is the diabetogenic effect?
GH opposing actions of insulin
What does serum concentration of GH binding protein reflect?
GH receptor density [[[BUT NOT GH density]]] → GH is unique to this because GHBP is the extracellular domain of the receptor protein that detaches.
What is the major endocrine role of IGFBP-4?
Inhibits IGF actions → serum concentrations of these are low
What happens when IGF and Insulin receptors form a hybrid?
It has low affinity for both → This in theory could be a cause for insulin resistance or Type 2 Diabetes
What secondary messenger system does GH trigger?
JACK/STAT or MAPK to stimulate growth (muscle and adipose)
What is the major endocrine role of IGFBP-6?
Only binds to IGFBP-2 and inhibits its action
Where is IGF receptor type 1?
Present in all tissues → EXCEPT liver → similar to insulin