Adrenal Cortex- hormones, Physiology Flashcards
1
Q
What is the function of Adrenal glands?
A
-
Inner Medulla (10%)
- secrets catecholamines: NE and Epinephrine
- concerned with the stress response
- concerned with the homeostasis of glucose and Na+
-
Outer Cortex (90%)
-
secretes adrenal steroids
- progesterone
- testosterone
- estradiol
-
secretes adrenal steroids
2
Q
What are the different layers of the adrenal cortex, what are their functions?
A
-
Outer zona glomerulosa
- Mineralocorticoid e.g. aldosterone synthesis
-
Middle zona fasciculata
- Glucocorticoids e.g. Hydrocortisone/Cortisol
-
Innermost zona reticularis
- Produces androgen precursors
3
Q
Glucocorticoids vs Mineralocorticoids
- examples and their action
A
- Glucocorticoids (e.g. Hydrocortisone/cortisol) affect carbohydrate and protein metabolism as well as regulating host defence mechanisms
- __except in replacement therapy glucocorticoids are mostly used for antiinflammatory and immunosuppressive properties
- Mineralocorticoids (e.g. aldosterone) Regulate water and electrolyte balance
- their action is not completely separated as some glucocorticoids have significant effects on water and electrolyte balance
- cortisol and aldosterone are equivalent on mineralocorticoid receptors however on sensitive tissue like the kidney 11-β-hydroxysteroid dehydrogenase convert hydrocortisone to the inactive metabolite of cortisone, thereby preventing the tissue from responding to hydrocortisone
4
Q
What are the key synthetic pathways for steroid production?
A
- Glucocorticoids are produced by cells of the zona fasciculata
- the synthesis is stimulated by adrenocorticotropic hormone (ACTH);
- Aldosterone is produced by cells in the zona glomerulosa,
- this is stimulated by angiotensin II
- the adrenal cortex only releases small amounts of androgens e.g dehydroepiandrosterone, androstenedione and testosterone and oestrogens e.g estradiol
- this only increases in adrenal disorders
5
Q
What is the effect of Glucocorticoid on the Gastrointestinal tract?
A
- decreases the calcium absorption in the GI tract and increases the excretion by the kidneys
- as it also causes can increase osteoblast and increased osteoclast activity, this may cause osteoporosis
6
Q
What is the effect of Glucocorticoid on the CVS?
A
- increased vasodilation
- decreased fluid exudation
7
Q
What is the effect of Glucocorticoids on inflammatory cells?
A
- Decreased entry of neutrophils from blood vessels and reduced activation of neutrophils, macrophages and Marcel
- secondary to decreased transcription of the gene for sanitation factors and cytokines.
- Decreased overall activation of T-helper (Th) cells
- reduce clonal proliferation of T cells and a switch from Th1 to Th2 immune response.
- helper T1 (Th1) cells tend to generate responses against intracellular parasites such as bacteria and viruses, Th2 cells produce immune responses against helminths and other extracellular parasites potentially allowing infection to continue while masked
- reduce clonal proliferation of T cells and a switch from Th1 to Th2 immune response.
- Decreased fibroblast function, less production of collagen and glycosaminoglycan and in some circumstances reduce healing and repair.
8
Q
What is the effect of Glucocorticoids on the mediators in the inflammatory and immune response?
A
- decreased production of steroids to reduce the expression of cyclooxygenase two.
- Decreased generation of many cytokines including
- IL-1, IL-2,IL-3,IL-4, IL-5, IL-6, IL-8, TNF-alpha, cell adhesion factors and GMCSF
- These are largely secondary to inhibition of gene transcription.
- Reduction in the concentration of complement compounds in the plasma.
- also, work to protect the body from infections and remove dead cells and foreign material
- Decreased generation of induced nitric oxide by nitric oxide synthase two (NOS2).
- Decreased histamine release from basophils and mast cells.
- Decreased IgG (IgG) production
- Increasing the size of anti-inflammatory factors such as IL-10, IL-1 soluble receptor and an annexin-1.
- ANX-1 and derived peptides inhibit eicosanoid synthesis, block leukocyte migration and induce apoptosis of inflammatory cells
9
Q
What is Annexin-1 (ANX-1)?
A
- an anti-inflammatory protein induced by glucocorticoids
- inhibit eicosanoid synthesis, block leucocyte migration and induce apoptosis of inflammatory cells
10
Q
How is the synthesis and release of Glucocorticoids regulated?
A
- synthesised under the influence of circulating ACTH secretion from the pituitary gland
- ACTH is also pulsatile and is regulated by Corticotropin-releasing hormone/factor (CRH/F)from the hypothalamus
- release of ACTH and CRF is inhibited by increasing glucocorticoid plasma levels
11
Q
What is the pattern of ACTH release
(Adrenocorticotropic hormone)
A
- peak release in the early morning at the time of waking
- nadir amount in the middle of the night
- increased secretion at the time of prolonged stress
- cortisol secretion shows the same pattern but the peak and nadir occurs ~ 2hrs later than those ACTH
- the pattern is related to sleep-wake patterns
- this is disrupted by shift work and long-haul travel
12
Q
Explain the transport of glucocorticoids in the body
A
- 10% of cortisol within the blood is in it’s free, active form, rest bound to plasma proteins
- Corticosteroid binding globulin (CBG) makes up 75% of protein-bound cortisol
- Albumin makes 15%
- Pregnancy is associated with an increased level of CBG which results in a compensatory increase in circulating plasma cortisol concentrations
- the amount of free cortisol remains stable
13
Q
What are glucocorticoids metabolic action?
- CHO
- Protein
- Lipid
A
- decreased uptake and utilisation of glucose and increased gluconeogenesis –> hyperglycaemia
- antagonises the effects of insulin at a cellular uptake of glucose
- stimulates glycogenolysis
- increased protein catabolism and reduced anabolism –> muscle wasting
- cortisol stimulates increased amino acid uptake –> gluconeogenesis
- inhibits amino acid uptake and protein synthesis, resulting in a net loss of skeletal protein
- redistribution of fat (Cushing’s syndrome)
- stimulates lipolysis and mobilization of fatty acids by potentiating the effects of GH and catecholamines
14
Q
What effects do Glucorticoids have on other hormones and in the body in general?
A
- Glucocorticoids are also able to stimulate aldosterone receptors
- (although aldosterone-sensitive tissues possess an enzyme, 11b-hydroxysteroid dehydrogenase1, which converts cortisol to inactive cortisone).
- Mineralocorticoid actions of glucocorticoids are only apparent at high concentrations.
- Another effect of excess cortisol is an enhanced vasoconstrictor response to catecholamines which results in increased blood pressure.
- Glucocorticoids can also produce psychological effects with possible feelings of elation or sedation.
15
Q
What is Cushing’s syndrome?
A
- abnormal distribution of lipid deposits caused by excessive exposure to Glucocorticoids, prolonged administration of glucocorticoid drugs, disease
- ACTH secreting tumour
Common side effects
- Osteoporosis
- increased susceptibility to infection
