Corticosteroids

Question 1

What is the precursor molecule of steroid hormones?

Answer 1

Cholesterol

Question 2

Corticosteroids can be classified into:

Answer 2

Gluco/mineralcorticoids

Question 3

Cortisol is what type of corticosteroid?

Answer 3

Glucocorticoids

Question 4

Aldosterone is what type of corticosteroid?

Answer 4

Mineralcorticoids

Question 5

Catabolism define

Answer 5

Breakdown of complex molecules in living organisms to form simpler ones

Question 6

Location of corticosteroids

Answer 6

Adrenal glands

Question 7

How is glucocorticoid release regulated?

Answer 7

Under the control of the hypothalamic- pituitary -adrenal (HPA axis)
Subject to negative feedback control

Question 8

Glucocorticoid has a negative feedback effect. Meaning?

Answer 8

It reduces further release of itself via a negative feedback effect at the level of anterior pituitary and hypothalamus

Question 9

Glucocorticoid release : mechanism

Answer 9

• Hypothalamus release CRH
• CRH has a +ve effect on the anterior pituitary: induces release of ACTH
• ACTH stimulates the adrenal gland

Question 10

ACTH

Answer 10

Adrenocorticotrophic hormone

Question 11

Cushing’s syndrome : state

Answer 11

Exposure to excessive levels of endogenous glucocorticoids

Eg. Possibly excessactivity in tumour in the pituitary or excess ACTH causing excess cortisol release

Question 12

Describe Cushing’s syndrome: effects

Answer 12

Moon face, with red cheeks
Easy bruising
Buffalo hump
Euphoria
Increased abdominal fat
Poor wound healing

Question 13

GRE

Answer 13

Glucocorticoid response element

Question 14

Corticosteroids act on what receptors? Located where?

Answer 14

Nuclear receptors

Located in the cytoplasm, where they can migrate to the nucleus and causes changes in gene transcription

Question 15

TM

Answer 15

Transcriptional machinery

Question 16

Molecular mechanism of action ofglucocorticoids upregulating TM

Answer 16

• section of the DNA associated with a GRE-binds to activated glucocorticoid receptor to bring about its effect
• TM goes along DNA operating at low levels
• glucocorticoid receptor moves into the nudeus, the nuclear receptors dimerise and bind to the gre—> activate/promote activity within gene TM

Question 17

Molecular mechanism of action ofglucocorticoids in repressing the activity of TF ( transcription factors) on the TM to reduce transcriptional activity

Answer 17

Some GRE are referred to as negative GRE (nGRE)
- TF in absence of glucocorticoid has stimulatory effect on TM
- when glucocorticoid receptor dimerises, moves into nucleus and binds to recognition site
- gets rid of TF, which then loses its stimultary effect on TM= reduced transcriptional activity

Question 18

Examples of therapeutically used glucocorticoids

Answer 18

• All readily absorbed from the get
  Hydrocortisone, synthetic glucocorticoids, dexamethason

Question 19

Hydrocortisone binds to? Metabolism?

Answer 19

Corticosteroid- binding globulin (transcortin) and to albumin in the blood and is extensively metabolised in the gut wall and liver

Question 20

Synthetic glucocorticoids bind to? Metabolism?

Answer 20

Bind to albumin but not to transcortin and are more slowly metabolised in the liver, giving them a longer duration of action

Question 21

Dexamethason

Answer 21

Glucocorticoid
Most potent and has the vast mineralcorticoid activity

Question 22

Topical administration of glucocorticoids can?

Answer 22

Deliver high concentration at a target site : w/o adversely/excessively increasing systemic circulatory levels of glucocorticoid—> reduced side effects associated with excess of glucocorticoid hormone

Question 23

Side effect of glucocorticoid therapy

Answer 23

Suppression of response to infection or injury
Cushing’s syndrome
Hyperglycaemia
CNS effects: euphoria and psychosis (short term administration) , depression w/ chronic treatment

Question 24

Sudden withdrawl of drugs after prolonged therapy may result in?

Answer 24

Acute adrenal insufficiency b/c of suppression of capacity to synthesis corticosteroids

—> takes time for body to return to situation where it responds normally to normal circulatory levels of cortisol