HPA axis

1. glucocorticoids
2. mineralocorticoids
3. secretes steroid hormones
4. divided into 3 zones
   1. Zona glomerulosa
      1. secretes aldosterone
      2. controlled primarily by renin angiotensin system, ACTH and other factors
   2. zona fasciculata
      1. secrete glucocorticoids, adrogens and estrogen
      2. controlled mainly by ACTH
      3. cortisol
         1. CGB
            1. corticosteroid binding globulin
         2. action

            Annotations:

            •    •Maintains life •Increases blood glucose – gluconeogenesis.   Also stimulates glycogenolysis.•Increases lipolysis•Decreases protein synthesis in muscle.   Increases protein metabolism in liver.•Anti-inflammatory, immunosuppressive.  Decreases response to infections, allergy.•Minor effect on sodium retention and potassium excretion.  
   3. zona reticularis
      1. secrete glucocorticoids, adrogens and estrogen
      2. controlled mainly by ACTH

1. noradrenaline
2. secretes catecholamines
3. under sympatheitc contro

1. subsequently releasing glucocorticoids from the adrenal gland

1. CRH-R1 accounts for all activity in HPA axis

Annotations:

• 266 aa, Located on chr 2p23  •400bppromoter at 5’end followed by 3 exons and 2 introns   •Exon 1 is not translated •Exon 3 encodes all known peptide products •POMC transcribed by a number of tissues in addition to corticotrophs in the pituitary   •Gene regulation- POMC mRNA levels are increased by CRH and inhibited by glucocorticoids   

Annotations:

•    CRH acts via type 1 CRH receptor increases and cAMP levels and increases POMC transcription. CRH, arginine vasopressin (AVP) and glucocorticoids all inhibit the mRNA expression of type 1 CRH receptor   Glucocortiocids stimulates POMC gene expression   

1. highest in the morning and lowest at night

1. Ectopic tumour (15%)
   1. tumours in lung, thymus or pancreas which secrete high levels of ACTH
2. pituitary (70%)
   1. tumours that secrete high levels of ACTH= high levels of cortisol
3. adrenal glands(17-19%)
   1. adrenal adenoma or carcinoma resulting in excess cortisol production
   2. ACTH independent Cushing's syndrome
4. Glucocorticoid excess
5. ectopic CRH production
6. other causes
   1. drugs- steroid treatments eg for asthma, arthritis
   2. Alcohol- pseudo-cushing's
7. symptoms/presentation
   1. osteoporosis
   2. diabetes
   3. myopathy

      Annotations:

      •  muscular disease in which the muscle fibers do not function resulting in muscle weakness
   4. receding hair
   5. mental disturbance
   6. buffalo hump
   7. acne
   8. truncal obesity
   9. hypertension

1. causes
   1. post partum haemorrhage
   2. severe head trauma
   3. non secreting pituitary tumours
2. Diagnosis: low ACTH (undetectable), low cortisol
3. clinical features
   1. pale patients
   2. coma due to hypoglycaemia because of the increased insulin sensitivity caused by cortisol deficiency
4. Treatment
   1. hydrocortisone 2-3 times a day to replace cortisol levels

1. 6 types of cells
2. POMC produced

1. during infection, lymphocytes release interleukins
   1. interleukins stimulate CRF release=ACTH release=increase cortisol level
      1. increases cortisol levels suppress lymphocyte function therefore act to limit immune reaction

1. Prednisone/prednisolone
2. dexamethasone
3. budesonide