Corticosteroids

Question 1

The pituitary-adrenal Axis:

Answer 1

Hypothalamus (releasing corticotrophin-releasing factor/hormone - CRF/H)
Anterior pituitary (releasing adrenocorticotrophic hormone -ACTH)
Adrenal cortex (cortisol)

Question 2

CRF/H are processed peptides act on

Answer 2

GPCRs in the anterior pituitary to stimulate POMC (Proopiomelanocorticotropin) –> POMC mRNA –> upregulation at the level of transcription

Question 3

POMC is processed to release:

Answer 3

ACTH and beta-LPH (beta-lipotropin)

Question 4

Cholesterol is the precursor of:

Answer 4

steroids

Question 5

Steroidogenesis pathways:

Answer 5

Cholesterol–> side-chain cleavage reactions generate pregnenolone –> produce progesterone/androgens/estrogen/mineralocorticoids and glucocorticoids

Question 6

Glucocorticoids bind to:

Answer 6

steroid hormone receptors –> interact with Hsp proteins (heat-shock p+) –> move into nucleus –> interact with specific hormone-response elements in DNA

Question 7

Suppression of the immune system by the glucocorticoids is due to:

Answer 7

Suppressing the activities of NF-kB (nuclear factor kappa B) and AP1 (Activator Protein 1) to repress specific gene expression

Question 8

Glucocorticoids regulated gene expression by:

Answer 8

Activating or Repressing the expression of many genes in the body

Question 9

Effects of glucocorticoids:

Answer 9

Metabolic actions

Anti-inflammatory actions

Question 10

Metabolic actions of glucocorticoids:

Answer 10

Increase of:
Glycogenolysis
Gluconeogenesis
Lipolysis
Lipogenesis
Protein catabolism

Question 11

The long-term consequence of protein catabolism:

Answer 11

Osteoporosis

Question 12

Anti-inflammatory actions of glucocorticoids:

Answer 12

Decrease production of:
Prostaglandins, cytokines, leukotrienes, and interleukins
Proliferation and migration of lymphocytes (T-Cells, B-Cells and NK cell)
Macrophage in the site of inflammation/tissues injury
phospholipase A2 (no COX enzyme form)

Question 13

Glucocorticoids drugs use for: ex. Dexamethasone)

Answer 13

Replacement therapy in adrenal insufficiencies
Anti-inflammatory and immunosuppressive action*
Myeloproliferative diseases
Respiratory distress syndrome in premature babies (increase synthesis of surfactant)

Question 14

High level of cortisol effect:

Answer 14

increased appetite, weight gain, muscles weakness, think skin, easy bruising, HTA, osteoporosis, diabetes.

Question 15

Glucocorticoids trigger also ____ in the tx of cancer (myeloproliferative disease)

Answer 15

apoptosis

Question 16

negative feedback of cortisol is due to:

Answer 16

Allosteric product inhibition

Question 17

Long-term high dose exogenous steroid lead to:

Answer 17

Shut down of HPA and adrenal atrophy