Class #13 - Corticosteroids

Question 1

Endocrine signalling?

Answer 1

Autocrine: same cell
Paracrice: Close cell
Endocrine: Communication by travelling in blood system. Acting on remote targets.

Question 2

Hormone def?

Answer 2

Chemical messenger that circulates in the body and has an effect on distant cells.

Question 3

Endocrine system general functioning?

Answer 3

Hypothalamus - > Pit. ->Thyroid/parathyroid/pancreas/Adrenal glands/Ovaries/Testes/etc.

Question 4

Adrenal axis?

Answer 4

Hypo: Corticotrophin releasing factor (CRF) or Corticotrophin releasing hormone (CRH) -> Anterior Pit.: Adrenocorticotrophic hormone (ACTH) -> Adrenal Cortex: Steroids (Cortisol)

Question 5

ACTH synthesis?

Answer 5

CRF ->GPCR in pit. stimulating POMC (peptide) synthesis -> beta-lipotropin (B-LPH) and ACTH

Question 6

ACTH effects?

Answer 6

1. Increase the availability of precursor molecules (cholesterol) in the inner mitochondrial membrane (IMM) of the adrenal cortex cells, allowing to make the desired steroids based on needs.
2. Increase the level of Cholesterol side-chain cleavage enzyme needed to initiate cleavage of cholesterol to Pregnelonone.

Question 7

ACTH synthesis?

Answer 7

CRF -> GPCR in pit. stimulating POMC mRNA -> preprohormone (ER) -> prohormone (Golgi) -> mature POMC hormone (peptide)-> beta-lipotropin (B-LPH) and ACTH

Question 8

ACTH affects which part of adrenal cortex?

Answer 8

Zona Fasciculata/Reticularis

Question 9

Prod. of aldosterone happens in which part of the adrenal cortex?

Answer 9

Zona Glomerulosa

Question 10

What all steroids hormones have in common?

Answer 10

four membered ring

Question 11

Glucocosticoids mec. of actions?

Answer 11

1. Binding with globulin forming (Corticosteroid-binding globulin (CBG) = Transcortin) carrying it around in circulation and releasing H to target cell.
2. Binds to steroid hormone receptors then interact with HSP (heat-shock p+) proteins to form complexes that move into the nucleus.
3. Interact with hormone-response elements inside DNA.
4. Altering the transcription of DNA

Question 12

Glucocosticoids mec. of actions?

Answer 12

1. Binding with globulin forming (Corticosteroid-binding globulin (CBG) = Transcortin) carrying it around in circulation and releasing H to target cell.
2. Binds to steroid hormone receptors then interact with HSP (heat-shock p+) proteins to form complexes that allow the Steroid + Glucosteroids receptor into the nucleus.
3. Interact with glucocorticoids response elements (GRE) inside DNA.
4. Activating or Repressing the transcription of DNA
5. Then, activation or repression of gene expression

Question 13

Reduction of immune system by glucocorticoïds?

Answer 13

Repressing both:
1. NF-kB (nuclear factor kappa B);
2. AP1 (Activator Protein 1)
That activate an immune response.
[- + + = -]
Mainly: Reduce the creation of Arachidonic acid

Question 14

Metabolic actions of glucocorticoids?

Answer 14

Purpose: regulate glucose level in body

1. Increase the expression/synthesis of the Enz. responsible for generating glucose: Glycogenolysis, gluconeogenesis, lypolysis and lipogenesis.
2. Increase p+ catabolism if lack fat of glycogen (neg. effect increase osteoporosis

Question 15

Anti-inflammatory. effect of gluco.?

Answer 15

1. Repression: NF-kB and AP1 inhibition = decrease IL-2 and plt activating factor (PAF)
2. Blocking of enz. that produce prostaglandins, cytokines, leucotriens and interleukins.
3. Decrease proliferation and migration of lymphocytes and macrophage to sites of inflammation.
4. Decrease production of phospholipase A2 by increasing the expression of lipocortin-1 or Annexin-1.
5. Indirect effect: decrease availability of Arachidonic acid
6. Direct effect: Decrease transcription of COX2 enz.

Question 16

Anti cancer effect?

Answer 16

Triggers apoptosis

Question 17

Gluco. as drugs (3)?

Answer 17

replacement therapy
anti-inflam.
Myeloproliferative diseases

Question 18

Cortisol vs dexamethasone differences in structure?

Answer 18

Dexa. as an extra

1. fluorine: more active in gluco/mineralocorticoid properties
2. methyl group: Increase activities, and prolonge T1/2

Question 19

Replacement Sx 1.Too low vs 2.Too high

Answer 19

1. hair, acne, greasy skin, irr. periods, tiredness

2. Increase appetite, weight gain, musc. weakness, thick skin, easy bruising, high BP, osteoporosis, db

Question 20

Use as anti-inflammatory effect?

Answer 20

allergie, eye disease, GIT (Crohn), acute resp. distress, infections, neuro, organ transplant, skin, joints, auto-immune disease, asthma,

Question 21

Use as myeloproliferative disease?

Answer 21

Triggers apoptosis

Question 22

Special cases of gluco. Dx use?

Answer 22

Premature babies: Delay labor (few hours) so surfactant can be made in babies lungs.

Question 23

Too much cortisol =

Answer 23

Cushing’s Syndrome: Weight gain, slow healing, fatigue, glucose intolerance, moon face, buffalo hump, weakness, hirsutism, high BP, rectile disf.

Question 24

Too much exogenous cortisol?

Answer 24

atrophy adrenals, hard to bring back