Endocrine System Flashcards
Where are mineralocorticoids produced?
Zona glomerulosa of the adrenal cortex
Where are glutocorticoids produced?
Zona fasciculata of the adrenal cortex
Give an example of a minerocorticoid
Aldosterone
What is the function of aldosterone?
Tubular reabsorption of Na+, Cl-
Tubular K+ excretion
Osmotic retention of H2O ; increase in blood pressure
Give an example of a glucocorticoid
Hydrocortisone
How is the synthesis and secretion of adrenal corticosteroids regulated?
Adrenocorticotrophic hormone (ACTH) stimulates synthesis and release of glucocorticoids (eg. hydrocortisone) from the adrenal cortex
Corticotrophin-releasing factor (CRF) from the hypothalamus regulates ACTH release and is regulated in turn by neural factors and negative feedback from plasma glucocorticoids.
Mineralocorticoid (aldosterone) release from the adrenal cortex is predominantly controlled by the renin angiotensin system
What is the mechanism of action of glucocorticoids?
Bind intracellular receptors which dimerise, migrate to the nucleus and interact with DNA to modify gene transcription and protein synthesis
Induce synthesis of some proteins and inhibit synthesis of others.
What is the mechanism of the anti-inflammatory/immunosupressive actions of glucocorticoids?
Inhibit the transcription of genes whose protein products are involved in the inflammatory response (COX-2)
Increase the expression of genes whose protein products are anti-inflammatory (annexin-1)
Describe the structure of the glucocorticoid receptor
The glucocorticoid receptor protein has 3 domains
Two zinc fingers are located in the central region and believed to wrap around the DNA helices.
There are also phosphorylation sites and regions of hormone-independent activation function (AF1) and hormone-dependent activation function (AF2) related to transcription.
What is the function of parathyroid hormones?
Controls blood calcium and phosphate levels
How does parathyroid hormone control blood calcium levels?
Stimulates release of Ca2+ from bone
Reabsorption of Ca2+ from urine
Absorption of Ca2+ from the gut
High plasma levels lead to decreased secretion via binding of Ca2+ to Ca2+ sensing GPCRs on parathyroid gland
Name two hormones secreted by the adrenal medulla
Adrenaline
Noradrenaline
What are the functions of adrenaline and noradrenaline?
- Control metabolism
- Cardiovascular function
- Response to stress
What are the effects of adrenaline?
- Increase in cardiac output
- Dilates bronchi
- Dilates pupils
- Relaxes gut smooth muscle
- Stimulates cortisol production/secretion
- Stimulates glucose release from liver
What types of hormones are released from the adrenal cortex?
Mineralocorticoids
Glucocorticoids
What are the functions of hydrocortisone?
Controls metabolism
Stress response
Suppression of immune response
What are the domains of the glucocorticoid receptor protein?
- Amino terminus (regulatory domain)
- Carboxyl terminus for hormone binding
- DNA binding domain (DBD)
What causes Addison’s disease?
Autoimmune disease or chronic inflammatory condition (e.g. TB)
What are the symptoms of Addison’s disease?
Low blood pressure
Weight loss
Depression
Malaise
What is the treatment for Addison’s disease?
Glucocorticoids used in replacement therapy
Glucocorticoids are used as antiinflammatory/immunosuppressive agents in what diseases?
Asthma
Eczema
Rheumatoid arthritis
How are glucocorticoids administered in asthma treatment?
Inhaler
Orally if inhaled treatment insufficient
How are glucocorticoids administered in eczema treatment?
Topically
What glucocorticoid is used in cancer treatment?
Dexamethasone
Why is dexamethasone used in cancer treatment?
Cancer patients undergoing chemotherapy are given dexamethasone to counteract certain side effects of their antitumor treatment
Why are glucocorticoids administered to patients with brain tumours?
To reduce cerebral oedema in patients with metastatic or primary brain tumours
What are the side effects of glucocorticoids?
Suppression of responses to infection
Osteoporosis (↓ activity of osteoblasts but ↑ activity of osteoclasts)
Cushing’s disease (iatrogenic)
Suppression of endogenous glucocorticoid synthesis
↓ fibroblast function, ↓ production of collagen and glycoseaminoglycans, reduced angiogenesis, fibrosis, therefore reduced wound healing and repair
When do side effects from glucocorticoids appear?
Often after prolonged use
What are the symptoms of Cushing’s disease?
Euphoria Buffalo hump Hypertension Cataracts Moon face, with red cheeks Increased abdominal fat Easy bruising Poor wound healing Thinning of skin Thin arms and legs (wasting)
What causes Cushing’s disease?
Caused by excessive exposure to glucocorticoids, but also
Increased free circulating levels Glucocorticoids owing to
Increased ACTH (pituitary tumour)
Increased cortisol secretion caused by adrenal tumour
There is an alcohol induced pseudo form of the syndrome
By what mechanism do mineralocorticoids act?
Binds to intracellular receptors
Receptor binding initiates transcription and translation of proteins resulting in :
↑ no. of Na+ channels in the apical membrane
↑ No. of Na+-K+-ATPase molecules in the basolateral membrane
What are the clinical uses for mineralocorticoids?
Main use in replacement therapy in Addison’s disease
Main agent fludrocortisone
Administered orally to produce a mineralocorticoid effect
Acts on intracellular receptors to modulate synthesis of various protein regulators
↑ Na+ reabsorption in distal tubes
↑ K+ and H+ efflux into the tubules
Used in combination with glucocorticoids in replacement therapy
What are the central tenets of the control of blood glucose?
Glucose is the obligatory source of energy for the adult brain
Physiological control of blood glucose reflects the need to maintain adequate fuel supplies in the face of intermittent food intake and variable metabolic demands
More fuel is made available by feeding that is required immediately and excess calories are stored as glycogen or fat.
During fasting, these energy stores are mobilised in a regulated manner
The most important regulatory hormone is insulin
Increased blood glucose stimulates insulin secretion
Reduced blood glucose reduces insulin secretion
What are the 4 main cell types in the islets of Langerhans?
Alpha cells
Beta cells
Delta cells
F cells
What is the function of the alpha cells in the islets of Langerhans?
Alpha cells secrete glucagon (increases blood glucose, breaks down glycogen into glucose)
What is the function of the beta cells in the islets of Langerhans?
Beta cells secrete insulin (decreases blood glucose, by facilitating glucose uptake into tissues and promotes the synthesis of glycogen from glucose)
What is the function of the delta cells in the islets of Langerhans?
Delta cells secrete somatostatin which inhibits the secretion of glucagon and insulin from a and b cells, respectively.
What is the function of the F cells in the islets of Langerhans?
F cells produce pancreatic polypeptide which regulates the secretion of digestive juices
What stimulates the secretion of insulin?
Presence, in the blood, of:
Glucose
Amino acids and fatty acids
Gastro-intestinal (GIT) hormones; incretins
What are the main incretins?
GLP-1 (glucagon-like peptide 1)
GIP (glucagon-like insulinotropic peptide)
What are incretins and what are their function?
Incretins are GI peptides which stimulate insulin secretion
Inhibit pancreatic glucagon secretion from a cells
Slow the rate of absorption of digested foods by decreasing gastric emptying
What tissues does insulin target?
Skeletal muscle
Adipose tissue
Liver
