Normal growth and clinical aspects Flashcards
What factors regulate growth?
Growth hormone release from AP
Thyroid hormones
Insulin
Sex steroids (especially during puberty)
Availability of nutrients
Stress
Genetics
What is growth hormone?
Growth hormone (aka somatotropin) is a peptide hormone released from the Anterior pituitary gland
What secretes growth hormone?
Somatotroph cells of the Anterior pituitary
What controls the level of somatotropin/GH release?
GH release is controlled via the release of two hypothalamic neurohormones with opposing actions:
1) GHIH - aka Somatostatin
2) GHRH
The balance of GHRH : GHIH is determined by the myriad of factors that impinge on the hypothalamus
In what two broad ways does Growth hormone affect our body
Regulates growth and development (indirect action)
Regulates metabolism (direct action)
Summarise the effect of GH on growth and metabolism?
Indirect action
GH necessary for child growth
Even in later life - GH necessary for maintenance and repair of tissue
Describe the role of Growth hormone in growth and development in children
GH is necessary for growth and development of the child.
Growth in the foetal period and the first 8-10 months of life is largely controlled by nutritional intake, but thereafter GH becomes the dominant influence on the rate at which children grow
GH requires permissive action of some other hormones
What are these?
GH requires permissive action of thyroid hormones and insulin before it will stimulate growth
Children with untreated hypothyroidism, or poorly controlled diabetes, have stunted growth despite normal GH levels.
What does Growth hormone stimulate growth at its target tissues?
Growth-promoting effect of GH is mediated through stimulation of both:
cell size (hypertrophy) and
cell division (hyperplasia)
in its many target tissues
Why is the growth-promoting effect of GH indirect?
The effect of GH on growth is achieved through the action of an intermediate known as insulin-like growth factor-I (IGF-1) aka somatomedin C as it mediates the action of GH
Why is IGF-1 described as ‘insulin-like’?
similar to pro-insulin, binds to receptors very similar to the insulin receptor and has hypoglycaemic qualities (hence “insulin-like”)
although latter action is limited to glucose uptake in muscle. Liver and adipose tissue have few IGF receptors
Where is IGF-1 produced?
IGF-I is secreted by the liver, and many other cell types, in response to GH release
and IGF-1 controls GH release through a negative feedback loop
What types of hormones are GH and IGF-1?
How do they travel around in the body?
GH and IGF-I are peptide hormones, but like steroid and thyroid hormones, they are transported in the blood bound to carrier proteins.
~50% of GH is in the bound form - so it acts as a reservoir for smoother release of GH to tissues (as it has a short half life when unbound)
How does IGF-1 provide negative feedback for GH?
Is there any other negative feedback mechanisms?
By inhibiting GHRH and stimulating GHIH
Growth hormone ALSO inhibits Growth hormone release from somatotrophs in AP
What is the effect of GH/IGF-1 on bone growth?
GH stimulates pre-chondrocytes in epiphysial growth plates to differentiate into chondrocytes
During this differentiation, the cells begin to secrete IGF-I and to become responsive to IGF-I
IGF-I then acts as an autocrine or paracrine agent to stimulate the differentiating chondrocytes to undergo cell division and produce cartilage, the foundation for bone growth
What is the effect of growth hormone on metabolism?
Direct effect
- Increases gluconeogenesis in liver
- Reduces sensitivity to Insulin of muscle/adipose tissue cells - less glucose uptake
- Increases sensitivity of adipocytes to lipolytic stimuli
- Increases amino acid uptake and protein synthesis in almost all cells
In the context of metabolism - compare GH to cortisol and insulin
Growth hormone has an anti-insulin effect in muscle/adipose tissue
In this sense - it is similar to Cortisol and different from Insulin
However - GH Increases amino acid uptake and protein synthesis in almost all cells = anabolic effect
(cortisol stimulates protein catabolism).
In this sense - it is similar to Insulin but different from cortisol
What does GH generally do to our metabolism
Stimulates the release of energy stores - to support growth