Describe the pattern of GH secretion through the life cycle…
incraease post-natal, plateau in childhood, peak in puberty, plateau in adulthood, decline in senescence
During puberty, what is increased in parallel to GH secretion?
IGF-1
GH is released in what fashion, making it a bad indicator of pituitary somatotroph function?
pulsatile variation throughout day
What 3 things broadly increased GH release?
Exercise, fasting, sleep
______ is the primary stimulator of GH secretion, while ______ is the primary inhibitor
Stimulator: GHRH
Inhibitor: Somatostatin (GHIH)
This enzyme regulates genes involved in growth and development, such as GH and GH Receptors.
It is stimulated by GHRH binding to Gs, and inhibited when somatostatin binds Gi.
PIT1 via CREB (Adenylyl cyclase, PKApathway)
What exerts negative feedback on the hypothalamus and pituitary to curb release of GHRH and increase somatostatin release?
GH, IGF-1
GH can induce the following growth actions indirectly via which action?
- ↑ protein synth
- ↑ Cell division
- ↑ Bone growth
IGF-1
GH has the following effects via direct or indirect action?
↑ blood glucose from liver
↑ lipolysis (blood FAs)
↓ Glucose uptake in muscle
Directly
GH has Anabolic or Catabolic on the below?
Muscle protein
AA
Fatty Acids
Muscle protein, amino acids: Anabolic
Fat: catabolic
In the fed state, protein supply is high with a mixed meal. What are the effects on GH, IGF and Insulin concentration? What happens as a result?
Increased GH, IGF, Insulin
Protein anabolism and growth
GH facilitates _____ to promote growth…
insulin
In the fed state with high CHO consumption, What happens to GH, IGF-1, and Insulin? What occurs as a result?
Decreased GH, NC IGF, Increased insulin
increased caloric storage
_____ suppresses GH release while increasing insulin in order to promote CHO storage…
hyperglycemia suppresses GH release
Describe the effect fasting has on GH, IGF and Insulin concentrations. What happens as a result?
Increased GH
Decreased IGF 1, insulin
Decreased anabolism and growth, increased caloric mobilization
Why does GH rise in the fasting state?
hypoglycemia stimulates GH secretion
In the fasting state, you have increased GH and Cortisol. This promotes synthesis of _____, which has what effect?
increased IGF-BP, limits IGF-1 availability to curb growth
Long bone growth will be stimulated by GH/IGF-1 as long as ____
growth plate stays open
Pubertal growth correlates with plasma level of…
IGF-1
This is a condition of excessive linear growth by increased stimulation of epiphyseal plates in the presence of GH excess.
gigantism
This is a condition where GH effects take place absent of linear bone growth, S/S include:
Gradual onset
deformity, large hands/feet
DM risk
viscera increase
Increased protein, decreased body fat
Acromegaly
What is responsible for 98 % of acromegaly, how is this detected?
somatotrope adenoma, detected via pituitary MRI
What two non-imaging diagnostics can help dx acromegaly?
Increased serum IGF-1
OGTT > 1 ng/ml
What are 5 etiologies of dwarfism during growth?
↓ GHRH, ↓ IGF-1 (pygmies), ↓ IGF-BP
Pituitary insufficiency
No response to GH (laron dwarfs)
Can growth occur absent thyroid hormone, but adequate GH? Why?
no, T3/T4 permit GH release
Cretinism occurs from inadequate _____
thyroid hormone
This hormone:
- ↑ bone turnover
- ↑ activity of chondrocytes and ↑osteoblast proliferation
- ↑ osteoclast action
- ↑ IL6, PGE2, IGF1 Receptors in bone (growth factors)
Thyroid Hormones
Prolactin secretion and mammary development relies on …
T3/T4
The following have what effect on GHRH release from the hypothalamus?
- Sex steroids
- Ghrelin
- Alpha-2 receptors
↑ GHRH
The following have what effect on GH secretion from the anterior pituitary?
- Glucocorticoids
- Thyroid hormones
- Ghrelin
↑ GH release
The following have what effect on somatostatin release from the hypothalamus?
- GC
- Glucose
- FFAs
- Beta 2 activation
↑ Somatostatin
The following have what effect on somatostatin release from the hypothalamus?
Ghrelin Arginine DA Serotonin ACh
Inhibit somatostatin
3 positive effects of glucocorticoids on GH signaling?
↑ GH gene expression, ↑ GHRH receptors, ↑ Ghrelin receptors
2 negative effects of excess glucocorticoids…
↑ somatostatin
↓ peripheral GH receptors
Cushings and Exogenous glucocorticoids can have what effect on growth?
muted GH secretion, suppressed growth
Adrenalectomy would have what two effects in the pituitary?
↓ GHRH and Ghrelin receptors
ACTH deficiency and hypocorticsolism are associated with…
↓ GH
Both low and high GC concentration have what effect on GH secretion?
↓ GH
Testosterone and GH have what synergistic effect in the liver?
↑ IGF-1 secretion
Estrogen has what effect in the liver?
↓ IGF-1 secretion
Muscle growth is a function of what three factors?
conditioning, nutrition, hormone signaling
Muscle strength increases rapidly with training.Results can occur how quickly?
hours to days
T/F?
Exercise increases glucose entry into cells absent of insulin
T
Infusion of ____ can stimulate muscle growth independent of training in the vastus lateralis and soleus…
amino acids
The below have what effect on mTOR
- Insulin
- IGF-1
- Amino Acids
- Phosphatidic Acid
Stimulate
The below have what effect on mTOR
- fasting
- low protein
- AMPK
- Myostatin
- GC
- Cytokines
Inhibit
mTOR has what effect on muscle growth?
increase muscle protein synthesis
This is a developmental gene that blocks muscle cell growth and differentiation.
It inhibits insulin action
myostatin