2-hypothalamus And Pituitary 1 Flashcards
Posterior pituitary doesn’t synthesize…
Hormones, but stores th3m
What are the 5 types of hormone secreting cells?
- gonadotrophs
- somatotrophs
- corticotrophs
- thyrottrophs
-lactotrophs
What hormone secreting cells are 1st to be affected by mechanical
lesions?
Gonadotrophs
Somatotrophs
Since they are posterolateral
Next are lactotrophs as they are scattered throughout the gland
Corticotrophs and thyrotrophs are most resilient since they are anteromedial
All hormones except for _____ & ______ function by stimulating other end8crine g”ands
GH
PRL
What are the 3 classes of anterior pituitary hormones?
POMC- ACTH
Lactogens- GH, PRL, (hPL*) are similar in structure
Glycoproteins-TSH, FSH, LH, (hCG*)
- a chains identical
- B chains differ
Describe the structure of growth hormone
GH is a 191 amino acid peptide
• Is similar in structure to PRL & human placentogen (hPL)
Where is growth hormone secreted?
By somatotrophs in the anterior pituitary
What happens when GH circulates in high concentrations?
High concentrations of GH can have PRL like effects
What is the half life of growth hormone?
Circulated unbound
Half life= 20-30 minutes
What does somatostatin do?
Inhibits secretion of growth hormone
Also known as GHIH
Summarize the mechanism of action of GHRH in the anterior pituitary
GHRH binds to receptor to increase cAMP, and via PKA there is an influx of Ca2+
This causes a release of GH via exocytosis
How does the somatotrophs respond to GHRH binding to the receptor?
GHRH receptor binding leads to increased cAMP and increased DNA transcription
This leads to increased GH production
What is the response of a somatotrophs to a somatostatin?
Somatostatin binds to receptor, and decreases cAMP and via PKA which is decreased and decreased Ca2+.
Inhibition of release 9f GH via exocytosis
What is the structure of the somatostatin?
It is a 14 AA peptide
What is the effect of growth hormone in target tissues?
Growth hormone stimulates Tyrosine kinase —> modulation of gene expression —> growth hormone effects
Describe the pulsatile secretion of GH
- Occurs in periodic bursts maximal peaks at night.
- Usually in stage 3 & 4 of slow wave of deep sleep
-Mean GH levels are highest at adolescence & level to baseline until senescence & then decline
What are the actions of GH?
GH is a major regulator of
- skeletal & soft tissue growth
- carbohydrate, lipid & protein metabolism. It’s overall effect is to increase blood glucose & thus known as diabetogenic
GH hormone exerts it’s actions by both
- direct
- indirect through IGF’s
What are the direct actions of GH in liver?
Increased glucose synthesis in liver to raise blood glucose
IGF synthesis in liver to increase IGF
Synth3sis of IGF-binding protein to increase IGF-BP
What are the direct actions of GH in adipose tissue?
Increased lipid breakdown to increase free fatty acids & glycerol
Decreased glucose uptake to increase blood glucose
What are the direct actions of GH in muscle tissue
Inhibits breakdown of proteins
Increases amino acid up take and protein synthesis
Glucose uptake decreased which increases blood glucose
What are the effects of GH on insulin?
GH increases blood glucose, which then increased insulin
Action of insulin is thought to be impaired due to increased FFA, exact mechanism not known
Insulin is required for growth
What is the importance of IGFs?
Also known as somatomedins
Structurally related to pro-insulin
• 6 different types of IGF’s, IGF1 is most important one
• IGF1(somatomedin C) is produced mainly in the liver in response to GH
• Bound to IGF-binding proteins – Longer half-life
• Bind to tyrosine kinase receptors of target cell membranes
Why are IGFs important?
Important for growth-promoting effects of GH
Summarize IGF function
Promote linear bone growth
Increase organ size & function
Insufficient synthesis of IGF’s can result in dwarfism
African pygmies & Levi Loran have this problem
What is the function of IGF-1 on Chondrocytes?
- AA uptake
- protein synthesis
- DNA & RNA synthesis
- Chondroitin sulfate
- Collagen
- Cell size & number
How is growth hormone regulated?
• It is regulated by 3 different hormones
- Growth hormone releasing hormone
- (GHRH) stimulates the release
- Somatostatin inhibits the release of GH
• 3rd mechanism is through both GH & IGF1(negative feedback to suppress GHRH & increase somatostatin release. This is a positive feedback effect)
• Thyroid hormone has permissive action on growth hormone • In hypothyroid children GH action is impaired
Give a general summary of hypersecretion of GH
Usually due to tumor in AP • It can result in either - gigantism or acromegaly • Gigantism occurs if it is before the closure of epiphyseal plates • The body grows in proportion • Achieve heights between 7 – 8 feet
Explain the clinical significance of acromegaly
If hypersecretion of GH occurs post-puberty results in thickening soft tissues & growth of skull bones resulting in
- growth of orbital ridges causing frontal bossing - prominent chin
- growth of mandible (prognathism)
- widening of teeth
-enlargement of hands, feet, ears & nose - all organ sizes are increased leading to
hypertension & heart failure • Diabetes
