What does growth depend on? and other influences?
Depends on growth hormone.
Other factors such as:
freedom from chronic disease (stressful environment)
and normal levels of growth-influencing hormones.
Name the 7 hormones regulating growth?
Thyroid hormone: stunted by hypothyroid.
Insulin: deficiency often blocks growth.
Testosterone: effects depends on presence of GH.
Estrogen: effects puberty years
Insulin-like growth factor-1 (IGF-1)
Calcitonin, parathyroid hormone & vitamin D
Reglation in the prenatal stage?
Regulation in the growth in infancy stage?
Regulation of growth in adolesence?
***GH secretion is higher at low ages***
Characteristics of the GH?
What is it also known as?
How many peptides long?
How much should you make a day?
How many genes encode it?
Peptide hormone is 191 AA protein.
Encoded by at least 7 different genes
What does the hypothalamus produce that effects the growth?
Growth hormone release hormone (GHRH)
Growth hormone inhibiting hormone (GHIH), also knwon as somatostatin (SS)
What does the anterior pituitary produce that effects growth?
What does the liver and other tissues produce that effects growth?
Insulin-like growth factors (IGF)
The GHRH and its receptor?
Interaction to produce GH
GHRH stimulates GH synthesis and secretion from somatotrophes.
GHRH binds to its receptor causing Ga protein to bind to GTP.
This activates enzyme AC (adenyl cyclase) producing cAMP (a secondary messenger).
Protein kinase A binds with cAMP allow the phosopholation of transcription factor CREB.
Turns on the gene and allows another transcription factor Pit-1.
Leaves the nucleus to produce proteins which then turns on the gene for growth factor.
The HP axis and regulation of liver IGF-1?
What is the half life of GH?
Growth hormone has a short half life (30mins)
How goes GH bind to its target cells?
what are these targets?
How many receptors can one GH molecule bind to?
Bones and muscles
One GH molecule binds to two receptors.
Binds to target cells
Stimulates growth (hypertrophy: increase size and volume of cells)
Stimulates cell reproduction :
increased rate of mitosis
Hyperplasia: increase the number of cells
GH function on metabolism?
Stimulates cell metabolism
Increase protein synthesis (increase amin transport and catabolism of protein)
Increase fat breakdown for energy.
What negative feedback is taking place for GH?
High level of IGF-1 stimulates GHIH and decrease secretion of GH.
High levels of GH inihibits GHRH.
How is GH released? ie. constant, bursts etc?
How much is secreted by men and women per day?
What (if any time) is GH levels released the most?
What factors effect GH production?
GH is released in pulsatile (Secreted in bursts)
500microg/day for men; 350 for women
GH is secreted in greater amount during sleep and changes in sleep pattern can affect GH release.
GH production declines with age.
High glucose levels inhibit GH secretion
What does GH do to aging?
Speeds it up.
What does GH do in the context of athletic ability?
Thought to promot athletic ability
What does GH do to other tissues (outwith muscles)?
It does no enlarge any tissues with GH excess
No penis increase
Why is IGF needed?
What is it similar to structurally?
Some GH are not direct and need IGFs to mediate their actions
Structurally similar to insulin.
What are the 2 genes that encode IGFs?
IGF-1 and IGF-2
What promotes the production of IGF-1?
Where is IGF-1 produced?
GH stimulates IGF-1 production
Produced in the liver
What responses does IGF-1 stimulate?
Such as linear bone growth and cell proliferation
Leading to soft tissue growth.
What is it called when you have normal production of GH but IGF-1 production is subnormal?
Some forms of dwarfism.
What is the condiion called when you lack pubertal surge of IGF-1?
How does IGF circulate the blood?
By binding to IGF binding proteins.
Many types: some enhance the action of IGF and some restrain IGF
The binding between IGF and IGFBPs?
High affinity and specificity
3 functions of IGFBP?
- Act as carriers of IGF in plasma
- Prolong the half-life of IGF in circulation
- Regulate IGF access to receptor in extracellular fluid.
How many types of IGFBP are there?
What percent of IGF-1 is bound in the body?
Most abundant protein
Accoutns for 80% of all IGF binding.
1:1 molar ration between IGF-1 & IGFBP
Promotes IGF mediated somatic growth.
Association with growth stimulation
Typically present in small amounts
High association with growth inhibition.
How does IGFBP-3 promote IGF-1 access to cellular receptor?
In the liver
IGFBP-3 binds to IGF
This complex can then trave to the IGF receptor.
Causing transcription of secondary growth hormones
How does IGFBP-1 inhibit IGF access to IGF receptor?
IGFBP-1 retains a higher binding affinity for IGF than the receptor itself.
It disallows access of IGF-1 to the receptor.
4 ways to increase GH production?
- Exercise regularly
- 8hrs of sleep.
- Protein-rich diet
- Avoid stress
What are the 3 GH associated disorders?
Deficiency in GH
Short stature (adult 4'10")
Occurs in children:
How does Dwarfism occurs?
GH absent during child's development
Hypopituitarism due to tumour.
Genetic causes due to mutations in GH1 gene, GHRH and Pit-1
How can you 'treat' dwarfism?
Daily injections of human growth hormone lead to modest improvements.
Excessive growth and height.
Continous secretion of GH
Open epiphyseal plate (affects bone growth length)
Occurs during childhood.
What can cause Gigantism?
Tumour formed by pituitary gland.
Secretes excessive gh/IGF-1
Acromegaly: Physical effects?
increased GH secretion in adults.
Closed epiphyseal plate.
Soft tissue harden:
Females start to look more manly.
What problems occurs withe gigantism?
Poor blood flow due to the large mass.
Increased muscle mass-weaker muscles as excess GH produces salt in muscle tissues.
Impaired movement: nerves getting crushed due to the weight.
What defects occur with acromegaly?
Heart tissue stiffen
Heart grows bigger in order to pump out sufficient blood.
Rib cage expanded
Diaphragm is stretched (thin and loses elasticity)