Flashcards in Endocrinology introduction Deck (25):
Chemical produced in ductless glands and secreted directly into bloodstream
Acts on cells or organs at a distant site
Acts on local cell or organ
Acts on cell which produced it
Chemical produced in glands with ducts and secreted to areas outside the bloodstream
Nuclear events of thyroid hormones
T3 and T4 enter cells by passive diffusion or active uptake
T4 deiodinated to T3 or rT3
T3 actively transported into nucleus, also binds to CTBP to enter the nucleus
T3 binds to thyroid receptors in nucleus already bound to regulatory TREs
TRAP protein stabilises TR, so it can interact and bind to DNA, using zinc fingers
Stimulates/inhibits target genes
Cellular events of thyroid hormones
T3 binds to membrane-associated receptors to activate sodium/potassium ATPase pump
Increased uptake of glucose and amino acids- required to burn to make ATP for mitochondria
T3 directly activates mitochondria- increase energy production
What is the main physiological action of thyroid hormones?
Increase basal metabolic rate
How do thyroid hormones affect calorigenesis?
Increase oxygen consumption in tissues, except brain, spleen, testes and anterior pituitary= increased heat production
Important for thermoregulation
Takes 4-5 days- involves synthesis of new sodium/potassium ATPase pumps and direct activation of mitochondria
How do cardiac glycosides inhibit thyroid hormones?
By blocking the sodium/potassium ATPase pumps
How do thyroid hormones affect carbohydrate, protein and fat metabolism?
Promote glucose uptake!
Increased GI glucose absorption and synthesis of metabolic enzymes
Sensitising tissues to insulin, catecholamines and growth hormone= promotes glucose uptake
How do thyroid hormones in the liver, fat and muscle cells?
In liver- increase in gluconeogenesis and glycogenolysis
In fat, liver and muscle cells- glucose utilisation in fat
Synthesis and lipolysis of fat
Increased oxidation of free fatty acids
How do high or low levels of thyroid hormones affect the synthesis and degradation of protein?
Low thyroid levels- synthesis and degradation of protein in equal measures
High thyroid levels- degradation predominates, leading to weight loss
What is the effect of decreased plasma cholesterol?
Increased liver uptake
Increased LDL receptors
Increased bile acid formation
How do thyroid hormones affect the maturation of the CNS?
Essential for normal CNS development during foetal and early neonatal life
T3 and T4 do not cross the placenta
Growth of cortical and cerebellar neurones and myelination of nerve fibres
How do thyroid hormones affect skeletal growth and maturation?
Synergistic effects with growth hormone- essential for bone growth and development
Essential for normal function of nervous cardiovascular systems, GI tract, teeth, skin and hair development
What hormones are involved in calcium homeostasis?
Parathyroid hormone increases plasma calcium
Calcitonin decreases plasma calcium
Vitamin D increases plasma calcium
Other hormones- oestrogens, GH, glucocorticoids
What is the action of calcitriol?
Free calcitriol and calciferol are lipophilic so cross the plasma membrane
Calcitriol binds to vitamin D receptors in nucleus
Vitamin D receptors heterodimerises with the retinoid X receptor
Stabilises reaction of VDR with DNA
Stimulation/inhibition of target genes
What are the actions of steroids within the cell?
Steroids are lipophilic and cross the plasma membrane
Bind to receptors outside the nucleus
Receptors dimerise= forms a homodimer
Homodimer enters nucleus
Expresses its zinc fingers
Binds to DNA and can either turn on or off transcription, mRNA, and protein synthesis
What are the actions of sex hormones within the cell?
Lipophilic and cross plasma membrane
Enter nucleus and bind to their own receptors in the nucleus
Binds to DNA and can either turn on or off transcription, mRNA and protein synthesis
What are the actions of glucocorticoid receptors?
Increase transcription of IL-4, 10, 13, TGF-B= anti-inflammatory
Receptors bind to and inhibit AP-1 and NF-KB, decrease transcription of IL-IB, TNFa, IL2, COX-2- pro-inflammatory
What are the anti-inflammatory and immunosuppressive effects of steroids within the immune system?
Decrease T helper cell action and reduced T cell clonal proliferation
Reduce number of circulating T and B lymphocytes and antibody production
Impair recognition responses in antigen presentation
Decrease leucocyte accumulation in inflamed area, macrophage release and phagocytic activity of macrophages
Increased neutrophil release from bone marrow
Decrease prostanoid and leukotriene activity and cytokine generation
Reduce complement component concentrations in plasma
Stabilise mast cell and lysosomal membranes
What are the anti-inflammatory and immunosuppressive effects of steroids outside of the immune system?
Direct vasoconstriction of small blood vessels= decreased vasodilation and fluid exudation
Reduce toxic oxygen radical generation from neutrophils and macrophages
What are the cellular actions of corticosteroids?
Switch off IL-1 and 2
CD4 helper cell then cannot form a primed CD4 helper cell
Then cannot form CD8 cells to produce cytotoxic T cells
Then cannot form B cells to produce plasma cells