GH, IGF and Prolactin Regulation of Growth Flashcards
GH is released from […] cells in the […] when stimulated to do so by […] neurons in the […] that release […] into the […].
Somatotrope
Anterior pituitary
Parvocellular
Hypothalamus
GHRH
Median eminence
What signals stimulate parvocellular neurons in hypothalamus to release GHRH into median eminence?
Exercise
Stress
Acute hypoglycemia
Aging
Starvation
What factors stimulate GH release?
What factors inhibit GH release?
GH release is primarily stimulated by […] and inhibited by […]
GHRH
Somatostatin
Describe how GHRH binds to somatotropes in the anterior pituitary and the signaling pathway that it initiates.
GHRH binds to a GPCR in the membrane of somatotropes. This GPCR signals via Gas subunit, resulting in stimulation of AC, increased cAMP and increased PKA activity. This will activate cAMP response element binding protein in nucleus and lead to enchanced transcription of gene that encodes pituitary specific transcription factor (Pit-1). Pit-1 activates transcription of GH gene and GHRH receptor gene. This results in increased GH production and increased ability of the cell to respond to GHRH.
Describe how somatostatin binds to somatotropes in the anterior pituitary.
Somatostatin from hypothalamus parvocellular neurons binds to a GPCR in the membrane of somatotropes. This GPCR signals via Gai subunit, resulting in inhibition of AC, decreased cAMP and decreased PKA activity and decreased intracellular Ca2+. This stimulates protein tyrosine phosphatase which decreases signaling that activates Pit-1. Somatostatin also binds to receptors coupled with K+ channels that results in membrane hyperpolarization and further reduction of Ca2+.
Once GH is released from anterior pituitary somatotropes, what are its effects in the body (general)?
- Adipose tissue –> increase lipolysis, decrease glucose uptake
- Muscle –> increase protein synthesis, decrease glucose uptake
- Hepatocyte –> increase production of gluconeogenic enzymes and production of IGF-1
Once IGF-1 is produced by hepatocytes in response to GH, what are its effects (general) on the body?
- Inhibit anterior pituitary somatotropes
- Stimulate Somatostatin producing neurons in hypothalamus
- Multiple effects on visceral organs, bone, cartilage, and such
Describe the manner in which / timing of day when GH is released.
Released in pulsatile bursts occurring mostly at night during slow wave sleep
Levels of GH increase during […], peak during […] and decline with […]
Childhood
Puberty
Age
What factors influence GH levels?
- Gender
- Nutrition
- Metabolic environment
- Hormones
- Renal and hepatic function
How does GH travel in the blood?
Bound to GH binding protein
How is GH handled once it binds to receptor on target organs?
Degraded in lysosome after receptor binding and internalization
What are IGFs?
Family of insulin-related peptides (insulin, IGF-1 and IGF-2)
Where can IGFs be produced?
Describe the levels of IGF-1 throughout lifetime.
Similar to GH
Low at birth, increase during childhood/puberty, decline by 3rd decade
IGF-1 is structurally most similar to […]
How can IGF-1 exist in the body?
Either free or bound to one of many binding proteins. Free half life about 15-20 min, bound to BP gives longer half life.
How are IGF-1 levels regulated in bone and in the reproductive organs?
How is the function of IGF-1 regulated?
IGF-BPs are primarily secreted by the […] but can also act […]
Liver (endocrine)
Locally (autocrine / paracrine)
Why are IGFBPs important?
Most circulating IGF-1 is bound to […] as a […]
IGFBP-3
Complex of IGF-1, IGFBP-3 and acid labile subunit (ALS)
What is the purpose of IGF-1 traveling in the blood as a complex with IGFBP-3 and ALS?
Sequesters IGF-1 in vascular system
Increases t1/2
Provides resevoir
Prevents excessive binding to insulin receptor
What controls the liver’s expression of IGFBP-3?
Levels of GH and insulin
What are the general functions of GH in the fed and fasted states?
Fed: promote growth and protein anabolism
Fasted: promote lipid consumption, sparing glucose for tissues that need it most and sparing protein digestion so as not to break down important tissues
- What is the most recognized general function of GH?
- How does it accomplish this effect?
IGF-1 Receptor
- What is meant by saying this recpetor is promiscuous?
- Describe its general structure and function
- What is the end result of ligand binding to this receptor?
- IGF-1, IGF-2 and insulin can all bind to it
- Hetero-tetramer, 2 extracellular alpha subunits that bind the ligand and 2 transmembrane beta subunits that are tyrosine kinase domains and transduce the signal via mulitple signaling proteins
- Activation of pathways involved in mediating growth and metabolic actions
The IGF-2 receptor is a […] receptor that binds to […] only
Mannose-6 phosphate
IGF-2
Review the effects of GH on the following organs in both the fed and fasted states:
- Adipose tissue
- Muscle
- Liver
- Bone, heart, lungs, kidney, pancreas, intestine, parathyroid, skin and connective tissue
- Chondrocytes
Review the effects of IGF-1 on the following tissues:
- Bone, heart, lungs, kidney, pancreas, intestine, parathyroid, skin and connective tissue
- Chondrocytes
- Muscle
What factors regulate human growth?
Genetics
GH and IGF-1
Thyroid hormones
Sex hormones
Glucocorticoids
Insulin
Nutrition
Short stature can be […] dependent or […] independent.
The most common cause of short stature is […] which is an […] disorder caused by a mutation in the […] gene
Achondroplasia
Autosomal dominant
FGF23
How do you investigate short stature?
What are the potential causes of tall stature?
Note that the GH excess when seen congenitally in children is called gigantism and when seen in adult life is called acromegaly
How do you investigate tall stature?
In what manner / when during the day is prolactin released?
Pulsatile rhythm of secretion: levels highest during sleep and lowest during waking hours
How is prolactin secretion regulated?
What stimulates prolactin release?
How does prolactin regulate its own production?
- GH function can be assessed via measurement of […] and with […] when levels are low or […] when levels are high
- Clinically, GH function is assessed by measuring […]
- baseline levels of GH and IGF-1; stimulation using GHRH, arginine, exercise; suppression with glucose ingestion
- longitudinal growth assessed by growth charts in childhood
