Week 9 Flashcards
(29 cards)
What are the three cortical zones?
Zona gomerulosa - Aldosterone
Zona fasciculata - Gulcocorticoids, adrenal androgens, and estrogens
Zona reticularis - adrenal androgens (DHEA and androstenedione), small amounts of oestrogen and glucocorticoids.
Why can only the zona glomerulosa convert corticosterone to aldosterone?
It is the only zone that normally contains aldosterone synthase.
What are adrenal steroids formed from?
Adrenal steroid hormones are formed from cholesterol via pregnenolone through a series of reactions that occur in either the mitochondria or endoplasmic reticulum.
What are mineralocorticoids?
Aldosterone and deoxycorticosterone
What are glucocorticoids?
Cortisol and coticosterone
What are androgens?
Dehydroepiandrosterone (DHEA) and androstenedione.
How is cortisol transported?
- Cortisol is bound to a globulin called transcortin (or corticosteroid-binding globulin (CBG)) which has a long half life
- small amounts of cortisol bind to albumin
- CBG is synthesised by the liver - production is increased by estrogen
- The unbound cortisol constitutes about 8% of the total and represents the biologically active form
What are the two regions of the adrenal glands and where do you find the adrenal gland in the body?
- Adrenal glands are located superior pole of each kidney.
- Two regions are Adrenal cortex (outer region encapsulating medullary region, secretes steroid hormones collectively known as corticosteroids)
- Adrenal medulla - inner region. Composed of modified sympathetic ganglion cells. Secretes catecholamines
Describe the cellular action of cortisol.
- lipophilic hormone
- by combing with specific intracellular receptors, this complex binds to specific regions of DNA to regulate gene expression
- Hormones are released into the plasma when they are made - very little storage in the adrenal cortex (cos its a steroid lol)
- Degraded in the liver- conjugated to glucuronic acid - excreted i faeces and urine (hepatic inactivation is depressed in liver disease and during surgery and stress)
What are the effects of cortisol on the metabolism in general?
- Antagonistic actions to insulin
- Primary effects on liver, skeletal muscle and adipose tissue
- Increases blood glucose by increasing gluconeogensis by liver, increased hepatic glucose output, decreased glucose uptake by muscle and fat, decreased glucose utilisation by cell but not by brain & heart (in adrenal insufficiency, fasting causes severe hypoglycemia)
- lipolysis from adipose tissue
- Protein catabolism to release amino acids
What are the hyperglycemic effect of cortisol?
- stimulates gluconeogensis
- enhances gene expression of the hepatic gulconeogenic enzymese - phosphoenolpyruvate carboxykinase, fructose-1,6-biphosphatase and glucose-6-phosphatase
- decreases GLUT 4 mediated glucose uptake in skeletal muscle and adipose tissue
- during interdigestive period (low insulin-glucagon ratio) it promotes glucose sparing
- It potentiates the effects of catecholamines on lipolysis, therby making FFAs available as energy sources
What are the effects of cortisol on protein metabolism
- Reduces protein stores in body except in liver (decreased amino acid transport, synthesis and increased catabolism)
- increases liver proteins (enhanced amino acid transport, synthesis, conversion to glucose)
- increases blood amino acids
- in hypercortisolism, protein depleted, muscle weak, immunity reduces, hair & skin thin, minor injuries cause bruises and ecchymosis, poor wound healing
What are the actions of cortisol on fat metabolism?
- Promotes mobilisation of fatty acids
- Increases free fatty acids in the plasma
- Increases oxidation of fatty acids in the cells
- Increases utilisation of FFA conserves glucose (in starvation)
- In hypercortioslism- excess fat deposition in the chest, head and upper back; but extremities are thin
Does cortisol increase bone resorption?
Yes
What are the actions of cortisol on skin, muscle and bone?
- Decreased keratinocyte division and collagen synthesis
- Increased protein catabolsim
What are the actions of cortisol on salt and water balance?
- Increased sodium reabsorption and increased potassium excetion
- Increased blood pressure
- Inhibits the secretion and action of ADH (in hypoadrenalism - inability to excrete water load)
What are the effects of cortisol on growth and development?
- Important in foetal cell differentiation and surfactant production
What are the anti-inflammatory effects of cortisol?
- Decreased T lymphocytes, increased neutrophils
- Inhibit cytokine production and antagonise macrophage activity.
- Reduced immunity, increasing red cells and platelets
Explain the regulation of Cortisol secretion.
- Hypothalamic-pituitary-adrenal axis
- CRH from hypothalamus
- Any type of stress perceived by various ares of brain-limbi system increases CRH
- ACTH from the pituitary.
- Cortisol - provides negative feedback to the pituitary and hypothalamus
What is the most important function of aldosterone?
- Regulation of the electrolyte (mineral salt) concentrations in EC, especially concentrations of sodium and potassium
Does Aldosterone have a specific plasma transport protein?
- No. It is rapidly cleared from the plasma by the liver because it lacks a specific plasma carrier protein.
Briefly explain the biosynthesis of aldosterone.
Cholesterol –> pregnenolone–>progesterone –> 11 - deoxycorticosterone –> corticosterone –> 18 OH corticosterone –> aldosterone
What are some of the actions of Aldosterone?
- Binds to the cytosol receptor of the target cell to induce synthesis of proteins which are involved in Na+ transport (Na+ channels in the luminal membrane)
- Acts on the distal convoluted and cortical collecting ducts. (increasing NA+ reabsorption and decreases Na+ excretion in the urine; increases urinary K+ excretion)
- It increases the number of apical membrane Na+ channel and this increases intracellular Na+
- Also increases the activity of several mitochondrial enzymes and this generates the ATP required to drive the membrane Na+/K+ pump
The aldosterone-stimulated proteins have two effects. A rapid effect and a slower effect. Explain.
The rapid effect of aldosterone is to increase the activity of epithelial sodium channels (ENaCs) (increasing the insertion of these channels)
A slower effect is to increase the synthesis of these ENaCs
