Growth hormones Flashcards
Tissue growth can arise as a result of:
- Increased cell size
- Increased cell number (division)
- Cell differentiation
Growth: Environmental Regulation
When id growth promoted?
Growth is promoted when nutritional environment is favourable
From the graph:
When the mother has a higher BMI, the foetus is exposed to more nutrients therefore the birth weight of the baby will be bigger
Growth: Describe temporal changes in growth
Looking at an average lifespan, there are periods of rapid growth, interspersed by slower growth and negative growth can be observed in old age
Rapid growth rate during infancy and adolescence, which slows in adulthood and decline with old age
Growth: Describe spatial Regulation
In humans, growth must occur in all tissues at the same rate and time
Growth is tightly regulated by a selection of hormones/growth factors:
- Growth hormone (GH)
- Insulin-like growth factors (IGFs)
- Insulin
- Other factors (less common/important, some cell specific)
Describe properties of growth hormone
- Gene for Growth Hormone located on chromosome 17.
- 191 amino acid peptide hormone.
- Molecular weight 20kDa.
- ~500ug of Growth Hormone is produced per day.
- Circulating levels 0-30ng/ml.
- Short half life ~20 minutes.
Typical serum Growth Hormone levels fluctuate over 24 hrs
(diurnal or daily pattern of secretion)
When hormone levels ar low, they fluctuate considerably but daily surges in growth hormone secretion occurs in a regulary pattern
Growth hormone secretion is secreted during sleep
They peak in the early morning just before awakening
The lowest levels of growth hormones are when you are awake during the day
External Regulators of Growth Hormone Secretion:
Name some stimulants
- physical stress (exercise)
- fasting (hypoglycaemia)
- deep sleep
External Regulators of Growth Hormone Secretion:
State some inhibitors
- psychological stress
- feeding (hyperglycaemia)
- hypothyroidism
- growth hormone itself
- ageing
Growth Hormone/Somatotropic Axis
Stimuli sent to hypothalamus→ Hypothalamus releases a hormonal factor to stimulate or inhibit the anterior pituitary→Releases factors that alther the physiological function of the target tissues
Describe Hypothalamic Stimulation
somatocrinin/Growth Hormone Releasing Hormone/(GHRH)→Stimulatory +
- 44 amino acid peptide hormone
- produced in hypothalamus: arcuate nucleus
- released from neurosecretory terminals of arcuate neurons
Describe Hypothalamic Inhibition
Somatostatin/Growth hormome inhibiting hormone (GHIH)→Inhibitory -
- Peptide hormone with 2 active forms ( one is 14 AA and the other is 28- amino acids)
- Produced in hypothalamus: periventricular nucleus
- Released from parvicellular neurons at median eminence
Describe pituitary regulation
GHRH and GHIH will both travel from the hypothalamus to the anterior pituitary via the hypothalamic-hypophysial portal system
There are cells within the anterior pituitary that express receptors for these 2 (peptide) hormones
There is a single receptor for GHRH and 5 receptors for GHIH (receptor 4 is not expressed on the surface of the anerior pituitary cells)
Pituitary Regulation
50% of pituitary cells are ‘somatotrophs’ (release Growth Hormone) and are located within the pars distalis
Physiological effects of Growth Hormone-Growth hormone has many target tissues:
- Liver
- Epiphyseal plate of the long bones
- Myocyte in muscle
- Adipocytes in fat tissue
Effects of growth hormone on target tissue depend on level of exposure: Describe acute insulin-like effects
Insulin like effects:
- Increase glucosen and amino acid uptake in muscle
- Increase lipgenesis in adipocytes
Effects of growth hormone on target tissue depend on level of exposure: Describe chronic insulin-like effects
Anti-insulin effects
- Decrease glucosen and amino acid uptake in muscle
- Increase lipgenesis in adipocytes
Where are anti insulin effects predominant?
In diseases where growth hormone levels are raised or when growth hormone is given as a therapeutic treatment over a long period of time
Growth hormone stimulates the release of two other growth factors from the liver:
Insulin-like growth factor I = IGF-I
Insulin-like growth factor II = IGF-II
Travel complexed with protiens (IGF binding proteins)
Similar in structure to pro-insulin
What is IGF-I?
- Peptide hormone – 70 amino acids.
- Bound to proteins (IGF-BP) in serum.
- Binds to IGF-IR (receptor tyrosine kinase/RTK).
- GH can sensitise cells to IGF-I (act synergistically).
- IGF-I has negative feedback control over GH production/secretion.
What is IGF-II?
- Peptide hormone - 67-amino acids.
- Bound to proteins (IGF-BP) in serum.
- Also binds to IGF-IR – may also bind IGF-IIR.
- IGF-II > IGF-I in circulation
What are Physiological roles of IGF-I?
- Foetal growth.
- Childhood growth – epiphyseal plates of bones.
- Adult metabolism.
What are Physiological roles of IGF-II?
- Foetal growth.
- Menstrual cycle – acts with FSH during folliculogenesis.
What are the metabolic effects of IGFs?
In addition to growth stimulation, IGFs have metabolic roles
IGF-I stimulates amino acid uptake in myocytes
IGF-II stimulates lypogenesis in adipocytes
acute→ indirect metabolic effects of GH via IGFs
chronic→ direct GH stimulation
Growth hormone, IGFs and ageing
In addition to growth stimulation, GH/IGFs have important evolutionary conserved roles in animal ageing:
If growth hormone signalling is inhibited (by mutating the recepotor for growth hormone or IGFs) these organisms live sigificantly longer than the normal controls
Not only do animals with reduced GH/IGFs live longer but they also display a more youthful physiology:
- Better mobility
- Improved metabolic profiles
- Leaner
- Better immune function
Growth Hormone Axis: Describe IGF Feedback
- Growth hormone can inhibit its own production and it can also feedback on the somatotrophic axis by inhibiting the release of growth hormone releasing hormone (GHRH)
- IGFs can feedback to to the somatotrophs in the anterior pituitary to directly inhbit growth hormone release and they can feedback to the hypothalamus to stimulate GHRH to inhbit growth hormone release from the anterior pituitary
Growth Hormone and IGF Feedback
- Low blood glucose (hypogycemia)
- This stimulates release of GHRH from the hypothalamus
- GHRH travels to the anterior pituitary and stimulates the release of hGH from the somatotrophs
- hGH and insulinlike growth factors speed up breakdown of liver (hepatocytes) gycogen to glucose, which enters the blood more rapidly
- Blood glucose level rises to normal (about 90 mg/100mL)
- If blood glucose continues to increase, hyperglycemia inhibits release of GHRH
What are the direct and indirect effects of growth hormone?
Direct→stimulates lipolysis
Indirect→ GH stimulates IGF release from the liver
