Unit 14 Flashcards
What 2 classes of hormone are derived from tyrosine?
Thyroid and adrenal medullary
Where are receptors for protein hormones typically found?
Cell membrane
Where are receptors for steroid hormones typically found?
Cytoplasm
Where are receptors for catecholamine hormones typically found?
Cell membrane
Where are receptors for thyroid hormones typically found?
Nucleus
What hormones are synthesised from cholesterol?
Steroid and thyroid
Which hormones are secreted from the anterior pituitary?
GH
TSH
ACTH
Prolactin
FSH/LH
Which hormones are secreted from the posterior pituitary?
ADH
Oxytocin
What hormones are secreted from the hypothalamus?
GHRH
CRH
TRH
GnRH
Somatostatin (growth hormone-inhibitory protein)
Dopamine (prolactin-inhibitory hormone)
What are the metabolic effects of GH?
Increased protein synthesis
Increased fatty acid mobilisation
Decreased glucose utilisation
What factors stimulate GH release?
Decreased BG
Decreased blood FFA
Increased blood amino acids
Starvation
Exercise
Testosterone
Sleep
GHRH
Ghrelin
What factors inhibit GH release?
Increased BG
Increased FFA
Aging
Obesity
Somatostatin
Exogenous GH
Insulin-like growth factors
Describe the structure of the thyroid gland
Composed of follicles filled with colloid
Lined with cuboidal epithelial cells
C cells - secrete calcitonin
What is the main constituent of colloid?
Thyroglobulin
What is the main influencer of iodine trapping in the thyroid?
TSH
How is iodide transported out of the cell across the apical membrane into the follicle?
Via iodine/chloride transporter - Pendrin
Briefly describe the steps of thyroid hormone formation
Thyroglobulin produced in thyroid cells, transported into follicle
Iodide transported into follicle via pendrin
Iodide oxidised by peroxidase and H2O2
Iodide binds with thyroglobulin - produces T4
Stored in follicle
Reabsorbed back into cell by pinocytosis
How do T3/T4 circulate in blood?
Small free fraction
Bound to thyroxine-binding globulin, thyroxine-binding prealbumin and albumin
What layer of the adrenal gland secretes aldosterone?
Zona glomerulosa
What stimulates aldosterone secretion?
AngII and potassium
Where is the majority of cholesterol for synthesis of adrenocortical hormones from?
LDLs
In which organelles are adrenal steroids synthesised?
Mitochondria and endoplasmic reticulum
Why doesn’t cortisol activate the renal mineralocorticoid receptor?
11B-hydroxysteroid dehydrogenase converts cortisol => less potent cortisone
Where is the main site of aldosterone action?
Principal cells in collecting tubules
What acid base disturbance is seen with aldosterone excess?
Metabolic alkalosis
H+ secreted in exchange for K+ in intercalated cells of collecting ducts
Where in the cell does aldosterone act?
Cytoplasm - mineralocorticoid receptor
What factors increase aldosterone secretion?
^K+
^AngII
What factors decrease aldosterone secretion?
^Na
^ANP
What effect does ACTH have on the rate of aldosterone secretion?
Very little, however, is necessary for secretion
How does cortisol affect CHO metabolism?
Stimulates gluconeogenesis - increases enzymes required for aa => glucose, mobilises amino acids, antagonises insulin’s antagonist effects on gluconeogenesis
Reduces cellular glucose utilisation - reduces GLUT4 translocation
How does ACTH stimulate steroid synthesis?
Activates adenyl cyclase, which activates cAMP
Activates protein kinase A - converts cholesterol to pregnenolone - rate-limiting step of steroid synthesis
What are the 3 cell types of the endocrine pancreas and what are their secretions?
Alpha cells - glucagon
Beta cells - insulin
Delta cells - somatostatin
PP cells - pancreatic polypeptide
Insulin half life
6 minutes
How is insulin degraded?
Insulinase (liver)
What is the main energy source for muscle, how does this change in different states?
Rest - fatty acids
Exercise - muscle contraction increases translocation of GLUT4 to membrane - glucose
Following meal - insulin allows transport of glucose into cells - glucose
How does insulin affect glucose handling in the liver?
Inactivate phosphorylase - prevents glycogen breakdown
Activates glucokinase - increases glucose uptake
Activates glycogen synthase - increases glycogen synthesis
How is glucose handling in the liver affected by lack of low glucose (and insulin) levels)
Phosphorylase activated - glycogen breakdown
Glucose phosphatase activated - allows release of free glucose
Briefly describe the mechanism of insulin secretion by the pancreatic beta cells
Glucose entters via GLUT-2 channel
Phosphorylated to glucose-6-phosphate (glucokinase)
Oxidised to ATP
Inhibits ATP K channels
Depolarises cell
Opens voltage-gated calcium channels
Exocytosis of insulin-containing vesicles
Other than glucose, what factors increase insulin secretion?
Amino acids (small effect when BG normal, when BG high potentiate glucose stimulation)
GI hormones - GLP-1 and GIP most potent (also gastrin, secretin and CCK)
Other hormones - glucagon, GH, cortisol, progesterone/oestrogen
What are the effects of glucagon on metabolism?
Increased glycogenolysis
Increased gluconeogenesis
Increases amino acid uptake by liver
Activates adipose cell lipase - increases fatty acids
Inhibits storage of triglycerides
What stimulates glucagon release?
Increased BG
Increased blood amino acids
Exercise
How does hypocalcaemia affect the nervous system and why?
Increased excitability
Increased neuronal permeability to sodium
How is calcium handled in the kidneys?
Protein-bound not filtered in glomerulus, rest is
99% reabsorbed
90% in PT, LOH and DT
10% in CD - more variable
What is bone composed of?
Organic matrix and calcium salts
What is the composition of organic matrix of bone?
90-95% collagen fibres
Remained ground substance - extracellular fluid, proteoglycans (chrondroiton sulphate and hyaluronic acid)
What ions are present in bone salts?
Calcium, phosphate, magnesium, sodium, potassium, carbonate
What prevents precipitation of hydroxyapatite in extracellular fluid?
Inhibitors - eg pyrophosphate
How is calcium salt deposition in osteoid regulated?
Inhibited by pyrophosphate
Levels regulated by tissue-nonspecific alkaline phosphatase, secreted by osteoblasts
What 3 substances are secreted by osteoblasts?
Tissue-nonspecific alkaline phosphatase - inhibits pyrophosphate
Nucleotide pyrophosphate phosphodiesterase 1 - produces pyrophosphate outside the cells
Ankylosis protein - transports pyrophosphate from inside to surface of cell
What is the main regulator of osteoclast activity? How does the regulation take place?
PTH
Indirectly - osteoblasts signal osteoclast precursors to mature - RANKL and macrophage colony-stimulating factor
How to osteoblasts prevent bone respiration?
Secrete osteoprotegerin (OPG) - binds RANKL and prevents binding to osteoclasts
How to PTH and Vit D affect osteoclast signalling?
Inhibit OPG production
Stimulate RANKL production
What regulates the rate of conversion of cholecalciferol to 25-hydroxycholecalciferol and where does conversion occur?
Liver
Feedback inhibition
What regulates the rate of conversion of 25-hydroxycholecalciferol to 1,25-hydroxycholecalciferol and where does conversion occur?
PTH
Proximal tubule of kidney
Where in the cell are vitamin D receptors found?
Nuclei
What are the effects of vitamin D?
Increases intestinal absorption of calcium and phosphorus
Decreases renal excretion of potassium and phosphorus
Promotes bone calcification in small quantities
Increases bone resorption in extreme quantities
How does vitamin D increase intestinal absorption of calcium?
Increasing formation of calbindin in intestinal epithelial cells
How does PTH affect the kidneys?
Increased calcium reabsorption
Reduced phosphate reabsorption
Increases reabsorption of magnesium and hydrogen ions
Decreases reabsorption of sodium, potassium and amino acids
Increased formation of 1.25-dihydroxycholecalciferol
Where does renal calcium reabsorption increase in response to PTH?
Thick ascending LOH
Distal tubules
How is PTH secretion regulated?
Calcium-sensing receptor
G-protein-coupled receptor
Stimulated by calcium - activates phospholipase C - increases inositol triphosphate and DAG formation => stimulates calcium release from intracellular stores => PTH secretion decreased
Where is calcitonin secreted?
Thyroid gland
Parafollicular (C) cells
How does calcitonin act?
Decreases osteoclast activity
Decreases osteoclast formation
What is the first line of defence against hypocalcaemia?
Buffer function of exchangeable calcium - predominantly in bones but also mitochondria especially of liver and intestine
