Adrenal Cortex & Axis

Question 1

Steroid Productions in the adrenal glands

how is ACTH acting: what does it stimulate

Answer 1

three groups
- glucocorticoids: cortisol
- mineralocorticoids: aldosterone
- androgens: testosterone and estradiol

cortisol and androgens - F and R layers

aldosterone: from the G

ACTH: stimulates release of cortisol and androgens via increasing cholesterol levels (HMG-CoA reductase and LDL receptors) and thereofre increaseing cortisol

the increased cortisol is a negative feedback: inhibits ACTH prodcution and CRH receptors on the pituitary (to stop ACTH production)

Question 2

Explain the Adrenal Axis

what upregulates cortisol release

Answer 2

the hypothalmus releases CRH (corticotropin releasing hormone)
- CRH enters portal blood of pituitary
- CRH is a peptide hormones: water soluable and membrane receptors

travels to the pituitary which releases ACTH
- ACTH is produced and released by corticotrophs in the pitutary (formed from the precursor hormone pro-opiomelanoncortin)

ACTH traves to the adrenal - and adrenal glands release cortisol (from Fasiculata and Reticularis layers)

cortisol exhibits its release process & then produces a negative feedback

Upregulation of cortisol release
(effecting hypothalmic release of CRH)
- stress,
- infection
- pain
- hypoglycemia
- trauma
- hemorrhage
- Sleep DECREASES cortsiol release

Question 3

Describe the significance of the pro-opiomelanocortin preprohormone

Answer 3

• secretes ACTH
• the melanocyte stimulation hormone
• N terminal & beta-LPH termial

melanoncyte stimulate + ACTH ride togehr: increase ACTH (addisons) = increase melaoncyte stimulation = tan

Question 4

Steroid Chemistry

Answer 4

all hormones from the adrenal cortex come from the same steroid structure: cholesterol backbone

• Glucocorticoids
• Mineralocorticoids
• Sex Steroids (androgens)

Aldosterone shares a simialr strucutre but…..
in the Glomerular layer: no 17-alpha hydroxlyase present to turn it into the cortisol and androgen type hormones: thuse it stays down the pathway to become alosterone

all start from cholesterol backbone to pregnenolone

the rate limiting step in steroid production is the production of pregnonelone (thats the precusor to all the steroids) because it needs ACTH to stimulate the conversion then the rest of hte pathways can happen in teh presense of the enzymes

Question 5

Function of ACTH from pituitary to adrenals

Answer 5

• stimulate syntehsis and secretion of hormones
• conver cholesterol into pregnenolone
• moblize cholesterol
• activate cAMP system (secondary messengers)
• helps maintain adrenal size

Question 6

Explain the regular release of cortisol from the body

compared to ACTH

what affects cortisol secretion

Answer 6

cortisol is released in a circadian rhythm
ACTH is pulsitile

Cortisol
- peaks at early morning 8am (max in the AM)
- dips at 2am
- lab test usually 8am and 8pm

Secretion of Cortisol affected by…
- sleep patterns
- light-dark exposure
- feeding times
- physical, psychological stress

when cortisol is secreted, it usally goes and binds to Transcortin (CBG) & albumin

Question 7

Function of Glucocorticoids
at carb metabolism
proteins
adipose
lymph
immune

Answer 7

• receptors for glucocorticoids found on almost every tissue
• this is cortisol
• once these are bound to their receptors at target tissues; DNA binding and interactions can occur
• these are the main feedback for the adrenal axis system (cortisol is the main negative feedback)

Action on carb metabolsim
- act as anti-insulin hormones: will increase blood glucose levels (a counter-regulator hormone)
- decrease the uptake of peripheral glucose
- increase the process of gluconeogenesis

Protein Wasting
- faciliate protien breakdown
- decrease calcium absorbtion and increase breakdwon
- inhibit amino acid uptake to muscles (cant use)

Adipose Tissue
- lipolytic (breakdwon adipose in the peripheral)
- increase fat depostion in teh trunk & face

Lymphatics
- involution of lymph system, thymus and spleen (decrease immune function)

Immune Function
- inhibit monocytes and antigen presentation
- inhibit inflammation by inhibiting leukotrience and protiglandins
- supressed COX2
- produces lymphopenia and eosinophilia (low lymphocytes, increase eosinophils)

Question 8

Other functions of glucocorticoids
skin
Lungs
CV

Answer 8

Skin and Connective Tissue
- reduces fiberoblasts and kerintocytes (thins)

Lungs
- stimulates surfacnt production!!! (can be given to moms for babies!)

CV
- increase contractility and vascualr reactivity

Question 9

Addisons Disease (primary adrenocortical insufficiency)

Answer 9

• lack of cortisol, lack of aldosterone due to destruction of the adrenal cortex from auto immune pathology (usually androgens spared or the production from elsewhere makes up for it)

Symptoms
- chronic fatigue
- low plasma Na+, high K+ (aldosteron lost)
- low BP

Treatment
- oral cortisol
- syntehtic mineralocorticoids

Question 10

Cushings Syndrome

Answer 10

excess cortisol secretion
results in…
- increase gluconeogensis, glucogenosis
- protein catabolism (breakdwon) in muscles
- lipolysis of fat in peripheral , build up in middle
- immune: increase nuetrophils, decrease ability to function
- osteoclastic activity
- decreased calcium
- CNS mood and cognition issues

Can be a result of…
- pituitary tumor: secreting ACTh = Cushings disease
- adrenal hyperplasis = excess cortisol

Symptoms
- thin arms, legs
- thick middle and face
- think skin ,bruses
- red cheeks
- striae

Treatment
- excision of the tumor (if pituitary - acth disease)
- rdation, chemo
- cortisol-inhibitnig drugs