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
