ACTH in the adrenal gland and Effects of Glucocorticoids Flashcards
ACTH originates from…?
Larger precursor molecule
- make large proteins and are cut at different spots to make different active proteins
What does POMC stand for?
Proopiomelanocortin
POMC is produced in …?
Corticotropes
Intermediary lobe
Arc
Keratinocytes
What are the three (tissue-specific) molecules that are the result of the cleavage during the post translational processing
ACTH
alpha MSH
BMSH
B-Endorphin
Cleaving both alpha MSH and CLIP give you ??
ACTH
when are precursor molecule cleaved??
post-translational processing
activated PKA is start 4 short term effects …
- LDLR
- CHO Esterase
- StAR
- P450scc
post translation processing is tissue-specific and result in …??
molecules with different biological activity
(ACTH, MSH, and B-endorphin
Increase of LDLR , result of activated PKA
helps LDLR go to the membrane to being LDL into the cell (bad cholesterol)
CHO Esterase
Breaks Cholesterol (LDL)
StAR
picks up free Cholesterol and takes it into the mitochondria (but must be phosphorated before doing so)
P450scc
breaks side chain of Cholesterol to make pregnenolone
occurs in the mitochondria
start of steroidogenesis
What is a long term effect of activated PKA in the nucleus
increase gene expression
+ making the proteins in the short term effects
Congenital Adrenal Hyperplasia (CAH)
- effect in cortisol synthesis
- lack of negative feedback
- 90-95% caused by mutation of P450c21
- Results: adrenal hyperplasia & excess production of adrenal androgen
- Problem»_space; female fetuses = masculinization (androgenization)
- Mild to sever»_space; complete absence of cortisol and aldosterone
- deficiency of mineralocorticoid
Corticosteroids
Steroid hormones (Glucocorticoids, mineralocorticoid, adrenal androgens)
Corticosterone
intermediary molecule in aldosterone synthesis pathway
- main glucocorticoid in birds, reptiles, amphibians
Cortisone
Cortisol synthetic
Dexamethasone
Potent synthetic corticosteroid
Name 4 Effects of Cortisol to increase blood glucose
- inhibits glucose uptake by peripheral tissues
- Myostatin»_space; break down proteins from the muscle to obtain Amino Acids
- Adipose tissues stimulates Hormone Sensitive Lipase (HSL)»_space; breaks down triglycerides to FA and glycerol
- Liver stimulates PEPCK and Glucose 6-Phosphatase (to do into gluconeogenesis)
Name two enzymes used in gluconeogenesis
PEPCK
Glucose 6- Phosphatase
(G-6-P)
In order for the Liver to reach glucose homeostasis it need to (3 specific things)
- Stimulate gluconeogenesis (PEPCK & G-6-P)
- increase glycogen deposit (make an easier way to get glucose)
- Decrease glycogen mobilization (not breaking down glycogen)
In order for the adipose tissue to reach glucose homeostasis it need to (2 things)
- Activate HSL
- inhibition of glucose uptake
In order for the Muscle to reach glucose homeostasis it need to (3 things)
- decrease synthesis of muscle fibers
- simulate myostatin
- inhibition of glucose uptake
Cortisol affects
every body system
has a widespread negative consequence
Negative affects from cortisol
- Endocrine system»_space; decrease (LH, FSH, TSH, GH)
- Immune system (anti-inflammatory action, immunosuppression)
- Brain/CNS (depression, psychosis, negative cognition, less activity at CNS)
Why would it be better to use a nonsteroidal anti inflammatory drug instead of a steroidal one?
Steroidal dug (cortisol) will block the entire inflammatory pathway
If you take a steroidal anti inflammatory drug what effects will it have??
You won’t have any signs of inflammation
NO….
- redness
- warmth
- Swelling
- pain
- loss of function
Regulation of immune system by glucocorticoids (cortisol) in INNATE IMMUNITY
Decreases …
(cell- mediate innate immune response)
- vascular permeability
- mast cell numbers
- APC numbers
(pro-inflammatory molecules)
- PG (prostaglandins) synthesis
- Cytokine Production
Regulation of immune system by glucocorticoids (cortisol) in ACQUIRED IMMUNITY
Decreases»_space;
- T and B lymphocytes in circulation
- Synthesis of immunoglobulins
Increases
- Lymphocyte apoptosis
An excessive amount of cortisol (effects on acquired immunity)
results to autoimmune diseases
- antibodies against own B cells
- Diabetes Mellitus Type 1
Cortisol Consequences of dysregulation of immune response
Exaggerated allergies
Autoimmune disease
- rheumatoid arthritis
- Type 1 Diabetes
Clinical use of Glucocorticoids
- dexamethasone
- triamcinolone
-prednisolone
Tropical, anti-itch medication
Autoimmune disease
chronic inflammatory diseases
Inhibition of the immune system after tissue transplant
Anaphylactic shock
Primary
when the original problem is at the endocrine gland (producing the hormone
Central or secondary
when the original problem is at higher centers (Brain or pituitary)
Hyperadrenocortism
AKA Cushing Disease
Increase cortisol or glucocorticoids
- ACTH- independent (most commonly iatrogenic)
- ACTH- dependent ( pituitaryprimary & non pituitary tumors secreting CRH/ACTH»_space; Cushing disease
Excess circulating Cortisol
(hyperadrenocortism) signs
- 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)
Cushing’s Disease
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
Addison’s disease
( Hypoadrenocorticism)
- cortisol deficiency
- expect high levels of ACTH
- primary hypoadrenocorticism»_space; low levels of adrenal cortex hormone
- associated with mineralocorticoid deficiency
- Causes»_space; autoimmune, infectious, congenital, iatrogenic & hyperpigmentation
