Hormonal regulation of growth Flashcards
- Describe the mechanism of synthesis and secretion of GH - Identify the factors influencing GH secretion - Describe the metabolic effects of GH - Describe the relationship between GH and insulin-like growth factors - Describe hormones affectiving growth beside GH - Identify factors influencing growth beside GH - Outline the types and pathophysiology of GH abnormalities
Hormones that stimulate growth
- thyroid hormone
- insulin
- testosterone
- oestrogens
- growth hormone -> principle
- insulin-like growth factor
- calcitonin, PTH, and vit D
Regulation at growth stages
Prenatal -> maternal factors, fetal insulin and IGF-1
Infancy -> genetic factors, GH production, thyroid hormone, IGF-1
Adolescence -> GH, insulin, IGF-1, and sex hormone surge
Growth hormone (GH)
- released from somatotrophs of anterior pituitary in response to release of GHRH
- regulates metabolism directly and indirectly
- manufactured as preprohormone in rough ER
- loaded into secretory granules in Golgi
Secretion of GH
- stimulated by GHRH release from arcuate nucleus
- inhibitory to somatostatin
- upregulation of cAMP, activation of PKA
- phosphorylation of calcium channels, drives exocytosis of secretory granules releasing GH
GHIH
- somatostatin is released from periventricular region
- somatostatin acts on somatotrophs
- somatostatin receptor acts as negative regulator of Adenylyl cyclase, decreasing cAMP, decreasing PKA, decreasing phosphorylation and decreasing intracellular Ca concentration
Decrease GH secretion
- IGF-1 -> primary mechanism negative feedback
- GH secretion negatively feeds back on somatotrophs
- hyperglycaemia
- obesity
Increase GH secretion
- stress
- high protein meals
- exercise
- hypoglycaemia
- ghrelin
Role of GH on liver in fed state
- increased RNA synthesis
- increased IGFs
Role of GH in muscle in fed state
- increased AA uptake
- increased protein synthesis
Role of GH in fed state in bone, heart and lung in fed state
- increased protein synthesis
- increased RNA synthesis
- increased DNA synthesis
- increased cell size and number
Roles of GH in Chondrocytes in fed state
- increased AA uptake
- increased protein synthesis
- increased RNA synthesis
- increased DNA synthesis
- increased collagen
- increased chondroitin sulfate
- increased cell size and number
Role of GH on adipose tissue in fasted state
- decrease glucose uptake
- increased lipolysis
Role of GH on muscle in fasted state
- decreased glucose uptake
Role of GH on liver in fasted state
- increased gluconeogenesis
Direct effects of GH
- binds directly to target cells (liver, muscle, adipose)
- antagonises the effects of insulin
- removal of pituitary (source of GH) -> facilitates better control of blood glucose in diabetes
- stimulates growth (hypertrophy)
- stimulates cell reproduction (hyperplasia)
Direct effects of GH on anabolic hormone
- increased AA uptake
- increased protein biosynthesis
- decreased proteolysis
Direct effects of GH on lipolytic hormone
- increased lipid degradation
- increased plasma fatty acid
Carbohydrate metabolism
- increased blood glucose
- increased hepatic gluconeogenesis
GH and negative feedback
One positive, two negative
- stimulates GHIH/somatostatin (high levels of IGF-1 and GH)
- decreases secretion of GH (high levels of IGF-1)
- inhibits GHRH (high levels of GH)
Insulin-like growth factor (IGF-1)
- GH stimulates release of IGF-1 (insulin-like hormone)
- regulates cell proliferation, cell differentiation and cell metabolism
- bound by IGFBPs and further associates with ALS when being transported in serum
- some cancers (prostate) can overexpress IGFBP and respond to IGFs
Other hormones that affect growth
- thyroid hormones
- sex hormones
- glucocorticoids
- insulin
How thyroid hormones affect growth
- promote ossification of bones and maturation of the epiphyses, neurological development in the foetus and children
- early deficiency in thyroid hormones causes congenital hypothyroidism
How sex hormones affect growth
- oestrogen stimulates release of GH and IGF-1
- oestrogen stimulates epiphyseal closure
- oestrogen and androgen stimulate bone growth, bone reaborption and remodelling
How glucocorticoids affect growth
- stimulate bone resorption and excess inhibits GH secretion
- excess of adrenal glucocorticoids cause growth to stop in addition, muscle wasting is observed
How insulin affects growth
deficiency leads to reduction in IGF synthesis and growth is slowed
Factors affecting growth besides hormones
- chronic disease
- genetic disorders
- psychological growth retardation
- malnutrition
GH abuse side effects
- carpal tunnel syndrome and fluid retention
- headache
- joint disorders
- lipoatrophy
- myalgia
- oedema
- paraesthesia
GH abnormalities
- pituitary dwarfism
- gigantism
- acromegaly
Pituitary dwarfism
- short stature
- proportional body
- affects 1/10000
- occurs in children
- modest improvement made with daily injections of GH
Gigantism
- GH excess before puberty
- body mass increase
- often result of tumour in pituitary glands
- glucose intolerance
- hyperinsulinaemia
- hypertrophy of viscera
- prone to infections
