Endocrine 11: Glucocorticoids Flashcards
Cells secreting Glucocorticoids
- Zona Fasciculata of the Adrenal cortex
- (small contribution from) Zona reticularis
hormones that make up glucocorticoids
- Hydrocortisone (cortisol): 95%
- corticosterone: 4%
describe the chemistry of glucocorticoid formation
- Cholesterol is freed from vacuoles
- it’s converted into pregnanolone in the inner mitochondrial membrane
- pregnanolone is converted in to 11-deoxycortisol in the endoplasmic reticulum
- 11-deoxycortisol is converted into Cortisol (glucocorticoid) in the mitcochondria
75% of Cortisol in the plasma is transported via
corticosteroid binding globulin (CBG)= Transcortin
15% of cortisol in the plasma is transported via
Albumin
presentage of free (unbound) cortisol in the plasma
10%
which form of cortisol is the active form
free (unbound) form
explain why there is very few cortisol in urine
because most of it is bound to a protein
which hormone stimulates production of CBG
Estrogen
When does CBG levels increase
during pregnancy
high levels of estrogen
When does CBG levels decrease
Liver Cirrhosis:
* impaired synthesis of plasma protiens (globulins)
Nephrosis:
* impaired nephron causing filtration of plasma proteins into urine
describe metabolism & excretion of Cortisol
Cortisol is conjugated into glucuronic acid, know as hepatic inactivation & excreted in urine
When does impairment of Hepatic inactivation of Glucocorticoids take place
- Liver disease
- during surgeory
- Other forms of stress
Describe Mechanism of Action of glucocorticoids
- hormone passes through cell membrane (because steroid)
- it binds to Cytoplasmic receptor forming hormone-receptor complex (HRC)
- HRC enters the nucleus and binds to Hormone response element (HRE) on the DNA to facilitate mRNA transcription
Actions glucocorticoids are divided into
- Permissive action
- Physiological action
- Pharmacological action
Enumerate & describe permissive actions of Glucocorticoids
Allows for glycogenolysis:
* Cortisol augments activity of Glucagon hormone onto the liver to break down glycogen
Allows for Lipolytic effect of catecholamines & growth hormone
Allows Vasoconstrictor effect of Angiotensin II & Catecholamines
Effect of Cortisol on Carbohydrate metabolism
Hyperglycemic:
Stimulate Gluconeogenesis:
* protein catabolism to release aa in the blood
* stimulate enzymes for hepatic uptake of aa & convertion into glucose
* increase Hepatic release of glucose in the blood
* excess glucose converted into glycogen
Decrease Muscle & adipose tissue affinity to glucose (Anti-insulin):
* Decrease affinity of insulin receptors to insulin
* Decrease mobility of glucose transporters from cytoplasm to membrane
* Decrease the phosphorylation of glucose into G6P
The only organs spared from anti-insulin effect of Cortisol are ___
Heart & brain
Effect of Cortisol on protein Metabolism
- Decrease protein synthesis
- Increase protein catabolism
- inhibit aa transportation into extraheptatic tissue
- Increase aa transportation into Liver
Effect of Cortisol on Fat Metabolism
- Lipolytic
- Increase FFA
- (in diabetics) increase Ketone bodies =Ketogenic
Effect of Cortisol on Appetite
Increase apetite by:
* Inducing Neuropeptide Y
* Suppressing CRH
Equivocal (decrease appetite):
* Stimulate Leptin Synthesis in adipocytes (negative feedback)
Effect of Cortisol on Cardiovasvular system
Required to maintain normal ABP:
* Positive inotropic effect on the heart through Beta adrenergic receptors
* Decrease production of VD prostaglandins to maintain VC tone
* Helps maintain blood volume by decreasing permiability of Endothelium
Effect of Cortisol on Kidney
- Increase GBF to increase GFR
- rapid excretion of water load
- Responds to Acid load by:
1. formation of ammonia from glutamate
2. increase urinary phosphate excretion by reducing its reabsorption
effect of Cortisol on CNS & Sleep
- Modulates Behaviour, mood & excitability
- Decrease REM sleep
- Increase Slow wave sleep
- Increase time spent awake
