Normal Growth and Clinical Aspects Flashcards
How is growth regulated?
GH from anterior pituitary Thyroid hormones Insulin Sex steroids Nutrient availability Stress Genetics
Growth Hormone is what type of hormone?
Peptide hormone
What controls the release of growth hormone?
Growth Hormone Inhibiting hormone (somatostatin)
Growth hormone Releasing Hormone
Growth hormone is also known as what?
Somatotropin
What categories does the activity of growth hormone fall into?
Growth and development (indirect)
Regulation of metabolism (direct)
Growth hormone requires what before it will stimulate growth?
Permissive action of thyroid hormones and insulin
What is the primary controlling factor of growth in early life?
Nutrition (8-10 months)
What is the role of growth hormone in adult life?
Maintenance and repair of tissue
How is the growth promoting effect of GH mediated?
Stimulation of cell size
Stimulation of cell division
(hypertrophy + hyperplasia)
What is the indirect function of GH on growth?
Intermediate - insulin-like growth factor-1 (IGF-1)
Somatomedin C
What is the hypoglycemic quality of IGF-1?
Limited glucose uptake in muscles
IGF-1 is secreted by what?
Liver and other cells in response to GH release
What is the effect of IGF-1 on GH?
IGF-1 levels inhibit growth hormone (negative feedback)
What is the role of IGF-II?
Limited to foetus and neonate
How are GH and IGF-1 unique?
Bound to carrier proteins, despite being peptide hormones
What % of GH is bound?
50%
What is the benefit of binding GH to carrier proteins?
Smooth outs the effects of the erratic pattern of secretion
Protects from excretion
What is the negative feedback effect of IGF-1?
- Inhibits GHRH
- Stimulates GHIH (somatostatin)
- Inhibits GH release from somatotrophs in pituitary
GH/IGF-1 effects on bone growth?
GH stimulates chondrocyte precursor cells in epiphiseal growth plate to differentiate into chondrocytes
What is the effect of IGF-1 on bone growth differentiation?
Cells begin to secrete IGF-1, and become more responsive to it
How does IGF-1 act as an auto/paracrine agent in bone growth?
Stimulating chondrocytes to undergo cell division and produce cartilage
What are the direct effects GH on metabolism?
Increases gluconeogenesis by liver
Reduces insulin ability to stimulate glucose uptake by muscle and adipose
Make adipocytes more sensitive to lipolytic stimuli
Increase muscle, liver, adipose uptake of AAs and protein synthesis
When is GH said to be diabetogenic?
When in excess
What is a diabetogenic?
Increases blood glucose
What does GH synergise with for its anti-insulin effect?
Cortisol
What needs insulin for glucose uptake?
Muscle and adipose tissue
What roles does GH share with insulin?
Increases aa uptake
Stimulates protein synthesis
What role does GH NOT share with insulin?
GH does not increase glucose uptake
GH has a main anabolic effect on what?
Everything but muscle and adipose tissue
What are the general roles of GH?
Mobilise glucose
Inhibits insulin action
Promotes lipolysis
Promotes aa uptake
When is GH secretion highest?
Teenage years
What is the nature of GH secretion?
Rapid and spontaneous up and down
When is the majority of GH released?
First 2hrs of sleep (deep delta sleep)
How much higher is GH secretion in children? When?
20x higher in children in the first 2hrs of sleep
What other GH related hormone has sleep inducing qualities?
Growth Hormone Receptor Hormone
How are GH levels evaluated?
Repeated measurements over 24hrs
How does IGF-1 vary through the day? What does this tell us?
Consistent
IGF-1 buffers the pulsatile variance of GH
What is the biggest influence on GH secretion?
Nutritional status
How does nutritional control mediate GH release?
Modulation of GHRH/GHIH
What are the stimuli that increase GHRH secretion?
- Actual or potential decrease in cell energy supply
- Increased amounts of AA in plasma
- Stressful stimuli
- Delta sleep
- Oestrogen and androgens
What is the effect of exercise on GH?
Increased Growth hormone secretion
Increased GH in delta sleep is related to what?
Growth spurts in children/adolescents
Tissue repair in adults
Which stimuli increase GHIH secretion?
- Glucose
- FFA
- REM sleep
- Cortisol
What hormonal effect is seen in REM sleep deprived subjects?
Increased GH secretion
Physiology of growth is affected by which factors?
Hormones
Nutrition
Genetics
Which hormones affect growth?
GH, IGF-1 Thyroid hormones Androgens & estrogens Glucocorticoids Insulin
What is the impact of sex hormones on growth?
Minor until puberty
What is seen in babies deficient in GH and IGF-1?
Born normal size as GH influence is minor
Which hormones may dominate intrauterine growth?
Insulin
IGF-II
When are thyroid hormones most important?
Development of the nervous system in utero and early childhood
What is the effect of thyroid hormones on GH/IGF-1?
Permissive effects
What is the effect of thyroid hormones on bones?
Ossification of cartilage
Teeth maturation
Contours of the face
Proportions of the body
What is cretinism?
Hypothyroid from birth
What is the effect of cretinism on growth?
Stunted growth due to TH’s permissive effect on GH
Retain infantile facial features
Why do injury and disease stunt growth?
Increased protein catabolism (glucocorticoid effects)
When are the periods of rapid growth in humans?
Infancy
Puberty
How does growth appear in infancy?
Episodic growth spurts of ~2.5cm
How does puberty cause growth spurts?
Androgens + estrogens produce spikes in GH secretion that ↑IGF-1
How do puberty hormones terminate growth?
Androgens and estrogens cause the epiphyses of the long bones to fuse
What are the most common causes of hypersecretion syndromes?
Endocrine tumours
What is gigantism?
Excess GH due to pituitary tumour BEFORE epiphyseal plates of long bones grow
Typically very tall
What is acromegaly?
Excess GH due to pituitary tumour after epiphyseal plates of long bones grow
Typically have enlarged hands and feet
What is the classic sign of acromegaly?
Adult foot growth
How are endocrine tumours treated?
Surgery
Somatostatin analogues
Dwarfism may be caused by what?
- GHRH deficiency
- GH secreting cell abnormality
- End organ unresponsive to GH
- Genetic mutations
- Precocious puberty
- Hypothyroid tumours
If dwarfism is hypothalamic in origin, how is it treated?
GHRH deficient - normal response to administered GHRH
If dwarfism is pituitary in origin, how is it treated?
GH secreting cells abnormal - less GH produced in response to GHRH
What is Laron Dwarfism?
High [GH]plasma, defective receptors prevent IGF-1 release
Why do Laron Dwarves have high [GH]?
Inability to release IGF-1 stops inhibition of GH
Why do pygmy peoples have dwarfism?
Mutation impairing cells ability to make IGF-1 in response to GH
How does precocious puberty cause dwarfism?
Excess GnRH release stimulates puberty by promoting sex hormone release.
These children have stunted growth because long bones fuse early
Why does hypothyroid cause dwarfism in children?
Loss of permissive effect of TH on GH
How do hypothyroid children differ from children deficient in GH?
Hypothyroid - retain infantile proportions
GH - proportionally normal