Normal growth and clinical aspects Flashcards
Where is growth hormone released from?
Anterior pituitary
What is another name for growth hormone?
Somatotrophin
do not confuse with somatostatin/GH inhibiting hormone
What type of hormone is growth hormone/somatothrophin?
Classic endocrine peptide hormone
What type of hormone is somatostatin/GHIH?
Neurohormone
Where is somatostatin/GHIH released from?
Hypothalamus
What hormones elicit a permissive effect for GH to stimulate growth?
Thyroid hormones
Insulin
What influences growth in the foetal period and the first 8-10 months of life?
Nutritional intake
What is the other name for insulin-like growth factor 1 (IGF-1)?
somatomedian
What mediates GHs effects on cell division?
IGF-1/somatomedian
What is IGF-1 similar to in structure?
Proinsulin
How is IGF-1 found to have hypoglycaemic qualities?
Causes glucose uptake in muscle cells, though not in liver and adipose tissue as they have few IGF receptors
What is the main tissue that secretes IGF-1?
Liver
What is IGF-II involved in?
Growth during foetal period and in neonate
What acts as a negative feedback signal for GH release?
IGF
GH itself
How does IGF act as a negative feedback signal for GH release?
IGF exhibits negative feedback on GH release both via inhibiting GHRH and stimulating GHIH/somatostatin.
What are the effects of GH and IGF on bones?
- GH stimulates chondrocyte precursor cells (prechondrocytes) in the epiphyseal plates to differentiate into chondrocytes.
- During the differentiation, the cells begin to secrete IGF-I and to become responsive to IGF-I
- IGF-I than 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 causes epiphyseal plates to close?
Sex steroid hormones during pregnancy
What are the direct effects of GH on the liver, muscle and adipose tissue?
- Increases gluconeogenesis by the liver.
- Reduces the ability of insulin to stimulate glucose uptake by muscle and adipose tissue.
- Makes adipocytes more sensitive to lipolytic stimuli.
- Increases muscle, liver and adipose tissue amino acid uptake and protein synthesis
What is basal [GH] in plasma in kids and adults?
0-3ng/ml
What is the 24-hour mean [GH] in both adults and in children/puberty?
2-4ng/ml in adults
5-8ng/ml in children and those going through puberty
By how much does GH secretion increase during sleep in children?
Approximately 20X ↑ in GH secretion in children during stages of deep delta sleep. General energy requirements low so energy diverted to growth.
About what % of GH is bound in plasma (even though it is a peptide hormone)?
50%
Why is GH and IGF unusual for peptide hormones?
Transported in blood with binding proteins
What is the physiological significance of bound GH in the blood?
May help prevent too much fluctuation in GH concentration in the blood
What stimulates an increase in GRHR secretion to induce GH secretion?
Actual/potential decrease in energy supply for cells Increased amino acids in blood Stress Delta sleep Oestrogen and androgens
What stimulates an increase in GRIR secretion to reduce GH secretion?
Glucose
Free fatty acids
REM sleep
Cortisol
What 3 factors influence growth?
o Hormones
o Nutrition
o Genetics
List the hormones involved in growth
o GH o IGF-I o Thyroid hormones o Androgens o Oestrogens o Glucocorticoids o Insulin
What hormones dominate intrauterine growth?
Insulin
IGF-II
Why are babies born with GH deficiency not born small?
Insulin and IGF-II dominate early growth
GH kicks in during childhood
What are some of the functions of thyroid hormones in growth?
Nervous system development in utero
Ossification of cartilage
Teeth maturation
Contours of face/body proportions
What causes cretinism?
Cretinism is a condition where children are hypothyroid from birth. They have retarded growth because of the loss of TH’s permissive action on GH. They retain infantile facial features = hypothyroid dwarf. GH levels are normal e.g. hypothyroid tadpoles never become frogs
What are the two rapid periods of growth in humans?
Infancy e.g. 2.5cm a day
Puberty
What causes growth in puberty, and how do hormones also influence the termination of growth?
Puberty: due to androgens and oestrogens, produce spikes in GH secretion that ↑ IGF-I →↑ growth. The same hormones also terminate growth by causing the epiphyses of the long bones to fuse. So, in normal puberty, before the epiphyseal plates fuse, GH/IGF-I promote bone elongation and increased height, weight and body mass. Sex hormones in the later stages of puberty act to close the epiphyses and hence stop bone elongation.
What hormones in the later stages of puberty cause the closure of the epiphyses to stop bone elongation?
Sex hormones
What is the difference between hypersecretion of GH in gigantism and acromegaly?
- Gigantism: excess GH due to a pituitary tumour before epiphyseal plates of long bones close→ excessive growth, may be more than 7ft tall (210cm), called pituitary giants.
- 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. However, can still grow in other directions and the characteristic features are enlarged hands and feet.
Whats the classic sign of acromegaly?
Feet keep growing
How is hypersecretion of GH caused by, and how is it treated?
Caused by excess GH due to a pituitary tumour
Surgery or somatostatin analogues
What can cause dwarfism?
GHRH deficiency Abnormal GH cell secretion End organ is irresponsive to GH (Laron dwarfism) Genetic mutations e.g. pygmies Precocious puberty Achondroplasia
Describe Larons dwarfism
End organ is unresponsive to GH (Laron Dwarfism) - Individuals may have ↑ [GH] in plasma. Defect GH receptor prevents IGF-1 release and peripheral tissues cannot respond to growth signal. Loss of IGF-1 inhibition of GH responsible for ↑ [GH] (remember negative feedback loop!).
What genetic mutation is seen in pygmies?
Pygmies have a genetic mutation that impairs the ability of cells to produce IGF-I in response to GH
What causes achondroplasia?
Achondroplasia is caused by a mutation in fibroblast growth factor (FGF) receptor
How does precocious puberty result in dwarfism?
Precocious puberty - excess GnRH release stimulates puberty via promoting sex hormone release. These children have stunted growth because long bones fuse early under influence of sex hormones.
