ACTH in the adrenal gland and Effects of Glucocorticoids

Question 1

ACTH originates from…?

Answer 1

Larger precursor molecule
- make large proteins and are cut at different spots to make different active proteins

Question 2

What does POMC stand for?

Answer 2

Proopiomelanocortin

Question 3

POMC is produced in …?

Answer 3

Corticotropes
Intermediary lobe
Arc
Keratinocytes

Question 4

What are the three (tissue-specific) molecules that are the result of the cleavage during the post translational processing

Answer 4

ACTH
alpha MSH
BMSH
B-Endorphin

Question 5

Cleaving both alpha MSH and CLIP give you ??

Answer 5

ACTH

Question 6

when are precursor molecule cleaved??

Answer 6

post-translational processing

Question 7

activated PKA is start 4 short term effects …

Answer 7

1. LDLR
2. CHO Esterase
3. StAR
4. P450scc

Question 8

post translation processing is tissue-specific and result in …??

Answer 8

molecules with different biological activity
(ACTH, MSH, and B-endorphin

Question 9

Increase of LDLR , result of activated PKA

Answer 9

helps LDLR go to the membrane to being LDL into the cell (bad cholesterol)

Question 10

CHO Esterase

Answer 10

Breaks Cholesterol (LDL)

Question 11

StAR

Answer 11

picks up free Cholesterol and takes it into the mitochondria (but must be phosphorated before doing so)

Question 12

P450scc

Answer 12

breaks side chain of Cholesterol to make pregnenolone
occurs in the mitochondria
start of steroidogenesis

Question 13

What is a long term effect of activated PKA in the nucleus

Answer 13

increase gene expression
+ making the proteins in the short term effects

Question 14

Congenital Adrenal Hyperplasia (CAH)

Answer 14

• effect in cortisol synthesis
• lack of negative feedback
• 90-95% caused by mutation of P450c21
• Results: adrenal hyperplasia & excess production of adrenal androgen
• Problem&raquo_space; female fetuses = masculinization (androgenization)
• Mild to sever&raquo_space; complete absence of cortisol and aldosterone
• deficiency of mineralocorticoid

Question 15

Corticosteroids

Answer 15

Steroid hormones (Glucocorticoids, mineralocorticoid, adrenal androgens)

Question 16

Corticosterone

Answer 16

intermediary molecule in aldosterone synthesis pathway
- main glucocorticoid in birds, reptiles, amphibians

Question 17

Cortisone

Answer 17

Cortisol synthetic

Question 18

Dexamethasone

Answer 18

Potent synthetic corticosteroid

Question 19

Name 4 Effects of Cortisol to increase blood glucose

Answer 19

1. inhibits glucose uptake by peripheral tissues
2. Myostatin&raquo_space; break down proteins from the muscle to obtain Amino Acids
3. Adipose tissues stimulates Hormone Sensitive Lipase (HSL)&raquo_space; breaks down triglycerides to FA and glycerol
4. Liver stimulates PEPCK and Glucose 6-Phosphatase (to do into gluconeogenesis)

Question 20

Name two enzymes used in gluconeogenesis

Answer 20

PEPCK
Glucose 6- Phosphatase
(G-6-P)

Question 21

In order for the Liver to reach glucose homeostasis it need to (3 specific things)

Answer 21

1. Stimulate gluconeogenesis (PEPCK & G-6-P)
2. increase glycogen deposit (make an easier way to get glucose)
3. Decrease glycogen mobilization (not breaking down glycogen)

Question 22

In order for the adipose tissue to reach glucose homeostasis it need to (2 things)

Answer 22

1. Activate HSL
2. inhibition of glucose uptake

Question 23

In order for the Muscle to reach glucose homeostasis it need to (3 things)

Answer 23

1. decrease synthesis of muscle fibers
2. simulate myostatin
3. inhibition of glucose uptake

Question 24

Cortisol affects

Answer 24

every body system
has a widespread negative consequence

Question 25

Negative affects from cortisol

Answer 25

- Endocrine system >> decrease (LH, FSH, TSH, GH) - Immune system (anti-inflammatory action, immunosuppression) - Brain/CNS (depression, psychosis, negative cognition, less activity at CNS)

Question 26

Why would it be better to use a nonsteroidal anti inflammatory drug instead of a steroidal one?

Answer 26

Steroidal dug (cortisol) will block the entire inflammatory pathway

Question 27

If you take a steroidal anti inflammatory drug what effects will it have??

Answer 27

You won't have any signs of inflammation NO.... - redness - warmth - Swelling - pain - loss of function

Question 28

Regulation of immune system by glucocorticoids (cortisol) in INNATE IMMUNITY

Answer 28

Decreases ... (cell- mediate innate immune response) - vascular permeability - mast cell numbers - APC numbers (pro-inflammatory molecules) - PG (prostaglandins) synthesis - Cytokine Production

Question 29

Regulation of immune system by glucocorticoids (cortisol) in ACQUIRED IMMUNITY

Answer 29

Decreases >> - T and B lymphocytes in circulation - Synthesis of immunoglobulins Increases - Lymphocyte apoptosis

Question 30

An excessive amount of cortisol (effects on acquired immunity)

Answer 30

results to autoimmune diseases - antibodies against own B cells - Diabetes Mellitus Type 1

Question 31

Cortisol Consequences of dysregulation of immune response

Answer 31

Exaggerated allergies Autoimmune disease - rheumatoid arthritis - Type 1 Diabetes

Question 32

Clinical use of Glucocorticoids - dexamethasone - triamcinolone -prednisolone

Answer 32

Tropical, anti-itch medication Autoimmune disease chronic inflammatory diseases Inhibition of the immune system after tissue transplant Anaphylactic shock

Question 33

Primary

Answer 33

when the original problem is at the endocrine gland (producing the hormone

Question 34

Central or secondary

Answer 34

when the original problem is at higher centers (Brain or pituitary)

Question 35

Hyperadrenocortism AKA Cushing Disease

Answer 35

Increase cortisol or glucocorticoids - ACTH- independent (most commonly iatrogenic) - ACTH- dependent ( pituitary**primary** & non pituitary tumors secreting CRH/ACTH >> Cushing disease

Question 36

Excess circulating Cortisol (hyperadrenocortism) signs

Answer 36

- skin thinning and alopecia (inhibition of collogen & hair growth) - centripetal obesity (effects regulation of triglyceride synthesis and adipose tissue in abdomen) - Dehydration (inhibition of H2O absorption) - Osteoporosis (effects CA 2+ deposition in bone) - Muscle weakness ( proteolytic effect to release AA)

Question 37

Cushing's Disease

Answer 37

Pituitary Tumors increasing ACTH-dependent Ectopic ACTH expression by nonpituitary tumor cells Bilateral hyperplasia of Zona Fasciculata and Zona Reticularis ACTH-independent causes include adrenal tumors

Question 38

Addison's disease ( Hypoadrenocorticism)

Answer 38

- cortisol deficiency - expect high levels of ACTH - primary hypoadrenocorticism >> low levels of adrenal cortex hormone - associated with mineralocorticoid deficiency - Causes >> autoimmune, infectious, congenital, iatrogenic & hyperpigmentation