Normal growth + clinical aspects Flashcards
Growth is regulated by what different factors (7)
Growth hormone (from AP) Thyroid hormones Insulin Sex steroids (mainly at puberty) Nutrient availability Stress Genetics
Growth hormone release is regulated by the balance of what 2 other hormones from the hypothalamus
GHRH
GHIH aka somatostatin
Growth hormone aka
+ secreted by
somatotropin
AP
Growth hormone has a DIRECT and INDIRECT action
- what does the indirect action do
- what does the direct action do
Indirect action - involved in growth and development
Direct action - regulates metabolism
Growth in the foetal period and 10 months of life is largely dependent on what
nutritional intake (NOT GROWTH HORMONE)
After what age does growth hormone become the dominant influence of growth
After 10 months
GH requires the PERMISSIVE action of what other things before it can stimulate growth, without these GH itself stunts growth
Thyroid hormones
Insulin
GH secretion continues throughout adult life - why?
essential in maintenance and repair of tissue
How does GH stimulate growth (2)
Stimulates hypertrophy + hyperplasia (cell division) in its target tissues
Growth hormone has a DIRECT and INDIRECT action:
Indirect action:
Describe how GH indirectly promotes growth + development (3)
-mention what intermediate is involved
Involves the intermediate, insulin-like growth factor-1 (IGF-1) aka somatomedin C
GH stimulates chondrocyte precursor cells in epiphyseal plates to differentiate into chondrocytes
During differentiation, the chondrocytes begin to secrete IGF-1 and become responsive to IGF-1
IGF-1 then acts as an autocrine/paracrine agent to stimulate the differentiating chondrocytes to undergo cell division + produce cartilage –> calcifies into bone
Insulin-like growth factor-1 (IGF-1) has a structure similar to what + what tissue does it have most effect on
Pro-insulin
Mostly causes glucose uptake in muscle as liver and adipose tissue have few IGF receptors
IGF-1 is secreted by what organ in response to GH release
Liver
How does IGF-1 control GH release
Via a negative feedback loop
-presence of IGF-1 feedbacks to the hypothalamus to inhibit GHRH and stimulate GHIH
Does GH travel freely in the blood
50% is bound to protein to provide a reservoir of GH
Somatostatin aka
+ secreted by
GHIH
hypothalamus
Somatomedin C aka
Insulin-like growth factor-1 (IGF-1)
-mediates GH
Apart from IGF-1 exhibiting negative feedback on GH release, what else exhibits negative feedback on GH release
GH itself has a negative feedback loop on its own release from somatotropin in the pituitary gland
What stimulates epiphyseal plates to close during adolescence (i.e. no further longitudinal growth)
Sex steroids - stimulate apoptosis of chondrocytes
Growth hormone has a DIRECT and INDIRECT action:
DIRECT action:
Describe 4 mechanisms that GH DIRECTLY regulates metabolism
- Increases gluconeogenesis by the liver.
- Reduces the ability of insulin to stimulate glucose uptake by muscle and adipose tissue.
- Promotes lipolysis to provide additional energy
- Increases amino acid uptake and protein synthesis in almost all cells = ANABOLIC effect
Growth hormone DIRECTLY regulates metabolism via 4 mechanisms:
- Increases gluconeogenesis by the liver.
- Reduces the ability of insulin to stimulate glucose uptake by muscle and adipose tissue.
- Promotes lipolysis to provide energy source
- Increases amino acid uptake and protein synthesis in almost all cells = ANABOLIC effect
What is common about the first 3 mechanisms?
What’s different about the 4th mechanism?
In all of these actions GH is releasing energy stores to support growth.
It is having an “anti-insulin” effect and synergises with CORTISOL in this respect.
GH is therefore said to be diabetogenic (increases blood glucose) when present in excess
4th mechanism - GH acts unlike cortisol and just like insulin
Are insulin and GH catabolic or anabolic hormones
anabolic
What does insulin stimulate that GH doesn’t
glucose uptake
Highest rates of secretion of GH occur during what years of life
teen
Secretion rate of GH undergoes rapid spontaneous fluctuations over 24 hours, however plasma levels of IGF-1 remain quite constant which suggests what
IGF-1 buffers the pulsatile variance in GH levels
As well as IGF-1 and GH itself controlling the release of GH, what else is GH secretion influenced by
Nutritional status
-mediates GH release via control of GHRH/GHIH release from hypothalamus
Stimuli that increase GHRH secretion (therefore increasing GH secretion)
- Decrease in energy supply to cells
- Increased plasma amino acids
- Stressful stimuli, e.g. infection, psychological stress
- Delta sleep
- Oestrogen and testosterone
How does decreased energy supply to cells stimulate GHRH secretion thus increasing GH secretion
GH is also needed for maintenance of tissues and their energy supply, so in situations where more energy is needed like fasting, exercise, cold weather, energy demand is increased which stimulates GH secretion
How does a rise in the plasma amino acid level after the digestion and absorption of a large protein meal affect GH secretion
Would stimulate an increase in GHRH secretion thus increasing GH secretion as GH promotes amino acid transport and protein synthesis by muscle and lover
Stimuli that increase GHIH secretion (thus decreasing GH secretion) (4)
Glucose
Free fatty acids
REM sleep
Cortisol
3 factors affecting growth
Hormones
Nutrition
Genetics
Name 6 hormones that affect growth
GH Insulin-like growth factor-1 (IGF-1) Thyroid hormones Sex steroids Glucocorticoids Insulin
What 2 hormones are associated with intrauterine growth
Insulin
IGF-II
What stages of life are thyroid hormones particularly important (2)
In utero - for development of nervous system
Early childhood
What is cretinism
Condition where children are hypothyroid from birth.
They have retarded growth because of the loss of thyroid hormone’s permissive action on GH
GH LEVELS ARE NORMAL
2 periods of rapid growth occur in humans - when are they
Infancy
Puberty
Hypersecretion of GH is usually due to what pathology
Endocrine tumours
What is gigantism
Excess GH due to a pituitary tumour BEFORE epiphyseal plates of long bones close –> excessive growth
What is acromegaly
Excess GH due to a pituitary tumour AFTER epiphyseal plates have sealed.
Long bones cannot increase so there is no longitudinal growth and no increase in height but non-long bones can still grow so can get big hands and feet
Classic sign of acromegaly
Large feet
Treatment of acromegaly (2)
Removal of tumour or somatostatin analogue
Features of hypothyroid children v GH deficient children
Hypothyroid - retain infantile proportions (i.e. still look like an infant)
GH deficient - proportionally normal, just small/short
