Growth hormone Flashcards
What are the different functions of the hypothalamus?
1) Secretes hormones to control the activity of the anterior pituitary
2) Produces ADH and Oxytocin
3) Control the sympathetic output of the adrenal gland
What are the hypothalamic hormones?
1) Thyrotropin-releasing hormone
2) prolactin-inhibiting hormone (dopamine)
3) Growth hormone-releasing hormone
4) Somatostatin (GHIH)
5) Corticotropin-releasing hormone (CRH)
6) Gonadotropin-releasing hormone (GnRH)
7) ADH
8) Oxytocin
What is the growth hormone?
- It is a single-chain protein of 191 amino acids (it consists of alpha-helical structures and has 2 cysteine bridges that stabilize the tertiary structure)
- It encourages growth directly/indirectly by stimulating the release of growth factors from the liver and muscle (indirectly like the release of IGF-1)
How is growth hormone released into the blood?
1) The hypothalamus will release GHRH (which will travel through the hypophyseal portal system)
2) The GHRH will attach to the G-protein-coupled receptors (GPCRs) on the pituitary
3) The receptor will activate adenylate cyclase
4) Adenylate cyclase will then convert ATP to cAMP which activates protein kinase A
- cAMP has a short and long-term effect:
1) The short-term effect is by increasing the Ca ion (through increasing the permeability of the cells) which will lead to the fusion of GH secretory vesicles with the cell membrane releasing the GH into the blood from the somatotroph cell
2) The long-term effect is the synthesis of mRNA from the DNA which is translated to GH (takes hours)
What is the mechanism of action of the growth hormone?
- JAK “Janus Kinase”/STAT “signal transducer and activator of transcription” pathway, where the signal is carried directly from the receptor to the nucleus by a single protein dimer
1) The ligand binding to the receptor leads to dimerization, the receptors themselves lack enzymatic activity, and thus they rely on JAK tyrosine kinase in relaying their signal
2) Once a GH binds, the receptor dimerizes and their associated JAK are activated by phosphorylation
3) The phosphorylated receptor will then bind to STAT
4) STAT will exert its effects directly in the nucleus as a forming an active transcriptional factor (inducing gene expression like IGF-1)
Where are the GH receptors present?
1) Muscle
2) Liver
3) Adipocytes
4) Bones
5) Cartilage
- Others
What are the different pathway by which the action of the GH is mediated?
1) JAK/STAT
2) MAPK pathway (mitogen-activated protein kinase)
3) PI3K/PKB pathway (phosphoinositol-3-kinase enzyme/protein kinase B)
What are the actions of growth hormones?
1) Binds to hepatic GH receptor, initiating:
1a) Insulin Growth Factor-1 generation
2a) Alteration of glucose metabolism (decreases its uptake and increases its production “by inducing glycogenolysis, and gluconeogenesis)
3a) Modulation of cell proliferation of gene
- The IGF-1 is primarily synthesized in the liver, mediating most of the growth-promoting actions of GH
- Metabolic actions of GH also affect carbohydrate, protein, and lipid metabolism
What are the various hormones that are involved in growth?
1) Growth Hormone (anabolic effect)
2) Insulin-like growth factor (can synthesize it directly and indirectly)
3) Thyroxine
4) Cortisol
5) Sex steroid
6) Insulin
What is the insulin-like growth factor?
- In humans, almost 80% of circulating IGF-1 is carried by IGFBP
- GH stimulates IGF-1 expression in the liver and other tissues including cartilaginous cell
- The IGF-1 receptor is a tyrosine kinase receptor, which undergoes ligand-induced autophosphorylation
- In addition to the insulin-like effects, IGF-1 can also regulate cell
growth and development, especially in nerve cells, as well as
cellular DNA synthesis
What are the functions of IGF-1?
- IGF-1 exists in two forms in the circulation either free (active form) or linked to binding protein
- It induces internal signals that:
1) Decreases apoptosis
2) Increases protein synthesis
3) Increases glucose metabolism
- This signaling results in cell multiplication which promotes visceral, muscle, and bone growth
- GH stimulates IGF-1 expression in the liver and other tissue, in acromegaly rising IGF-1 causes a generalized increase in skeletal, muscular, and visceral growth
What is the effect of GH on skeletal muscles?
1) Inhibits the uptake of glucose by muscle cells which inhibits glycolysis
2) Increases amino acid transport, stimulating protein synthesis, increasing the fat-free lean tissue
3) It stimulates muscle growth (by increasing energy expenditure)
What is the effect of GH on adipocytes?
1) Initially insulin-like, then Anti-insulin effect
2) It increases lipolysis by stimulating hormone-sensitive lipase, which will increase the free acids in the circulation, using it as fuel
3) Promotes fatty acid oxidation (giving acetyl CoA and glycerol “goes to the liver and it is converted to glucose”)
4) It decreases the transport of glucose into the adipocytes
- The acetyl-CoA goes for ketogenesis, while the glycerol goes for gluconeogenesis
What is the effect of GH on the liver?
1) In the fasting and stress state GH increases fatty acid oxidation to acetyl CoA this acetyl-CoA and the one produced by the adipocytes promotes ketogenesis (which occurs in the liver)
2) The produced Glycerol will become a substrate for gluconeogenesis
3) GH will inhibit glycolysis
What is the effect of GH on protein metabolism?
1) It increases amino acid transport
2) Increases the RNA translation, leading to the protein synthesis by the ribosomes
3) It decreases the breakdown of proteins
4) Increases the nuclear transcription of the DNA
- This will all lead to increased muscle mass, cardiac hypertrophy, and increased osteogenesis
