Download Adrenocortical hormones –outline

Adrenocortical hormones
The adrenal cortex synthesizes three kinds of steroids:
1.glucocorticoids（GCS）,in human ,hydrocortisone(cortisol) is the main glucocorticoid ,
it was produced and released from the cells of zona fasciculata of adrenal cortex.
2.mineralocorticoids , aldosterone is the main mineralocorticoid, it was produced and
released from the cells of zona glomerulosa of adrenal cortex..
3.sex hormones, include androgen and estrogen , produced and released from the cells of
zona reticularis of adrenal cortex.
Glucocorticoids（GCS）
physiological effects
1. Effects on carbohydrate: They can increase the blood glucose level by the following ways :
①stimulate glyconeogenesis from amino acid, lactic acid and glycerol.
②stimulate glycogen deposition in liver ,
③in periphery tissues, it can decrease the oxidation and utilization of glucose by inhibiting
the transport and uptake of glucose by muscle cells.
2. Effects on protein metabolism:
① Stimulate protein and RNA synthesis in the liver.
② Have catabolic effects in lymphoid and connective tissue, muscle, fat, and skin.
③ Supraphysiologic amounts: lead to decreased muscle mass and weakness.
3. Effects on fat metabolism:
① promote the lipolysis in adipocytes with increased release of fatty acids and glycerol
into the circulation.
② it can cause dramatic redistribution of body fat.
4. Effects on electrolyte and water balance :
Pharmacological effects
1. anti-inflammatory effects: three characters
①Glucocorticoids have strong anti-inflammatory action,
②This effect was nonspecific, they are effective to all kinds of inflammation such as
those caused by radiant, mechanical , chemical, biological, infections and immunological
stimuli.
③They are effective to both the early phase and later phase of inflammation:
 Mechanism of anti-inflammatory action
1) Regulating the production of cytokine, and reducing the cell response of
inflammation. GCS can inhibit the production of some pro-inflammatory cytokine such as
IL-1, IL-3, IL-8, TNF-α（tumor necrosis factorα）and GM-CSF（granulocyte-macrophage
colony stimulating factor）,they can also induce the production of some anti-inflammatory
cytokine such as IL-10.
2) Inhibiting the metabolism of AA and inhibiting the production of PGs and LTs
Membrane phospholipids
GCS
induce lipocortin-1 (－)
PLA2
Arachidonic acid（AA）
COX
NSAIDs
LOX
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Prostaglandins（PGs）
Leukotrienes（LTs）
3)↓ activity of NOS（nitric oxide synthase）→ ↓ NO
4) inducing ACE（angiotensin converting enzyme）→↑the degradation of bradykinin
2. immunosuppressive effects:
1) Inhibiting phagocytosis and management of macrophages on antigen
2) promoting the redistribution of lymphocyte in human blood→↓lymphocytes in
circulation
3) small dose : inhibit the cellular immunity
large dose: inhibit the humoral immunity
3. anti-shock effects: Supralarge dose of GCS can be used to treat any kind of shock,
especially infectious-toxic shock.
1) relaxing the smooth muscle of spasmodic vessels and enhancing the contractility
of myocardium
2) reducing the sensitivity of some vasoconstrictive substances on vessel
3) stabilizing the lysosomal membrane and decreasing the production and release of
myocardial-depressant factor（MDF）
4)enhancing tolerance of body to bacterial endotoxins
4. effects on blood and hemopoietic system:
1) stimulate hemopoiesis →↑RBC, PLT, and Hb（hemoglobin） in circulation.
2)↓ lymphocytes, monocytes , eosinophils and basophils in blood
3) Increase the number of neutrophils but inhibiting their function
2. other effects:
 Central nervous system: stimulate the CNS and may cause euphoria, excitement
and insomnia.
 Digestive system: stimulate the secretion of pepsin and gastric acid, and may
induce peptic ulcer.
Clinical uses
 replacement therapy in small dose
acute or chronic hypofunction of adrenal cortex (such as addison’s disease), post
adrenalectomy, hypofunction of anterior pituitary .
 Severe infection and inflammation
 severe acute bacterial infections : Fulminant epidemic meningitis, toxic pneumonia,
toxic dysentery, scarlet fever and so on. Under such circumstance, large-dose, short-term
treatment of GCS may help patients go through dangerous stage
attention: must be combined with large-dose of effective antibilateral agents
 prevention of some inflammatory sequela: iritis, keratitis, retinitis, tuberculosis,
meningitis, testitis. GCS must be used during the early stage of inflammation
 Allergic and autoimmune diseases
allergic diseases: hay fever, serum sickness, urticaria, contact dermatitis, drug
reactions ,bronchial asthma, angioneurotic-edema.
Autoimmune diseases: such as rheumatic arthritis, rheumatic fever, systemic lupus
erythematosus , autoimmune hemolytic anemia, rejection in organ transplatation,
 Shock
infectious-toxic shock(first choice), anaphylactic shock, cardiogenic shock ,
hypovolemic shock and so on..
 Blood disorders
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Acute lymphatic leukemia, aplastic anemia, thrombocytopenia, granulocytopenia.
 topical uses
some skin diseases and some eye diseases
GCS are remarkably effacious in the treatment of a wide variety of skin disorders such
as contact dermatitis, eczema.
Adverse reactions
 continued use of supraphysiological doses of GCS
 Iatrogenic Cushing’s syndrome: mainly caused by metabolism disorder of lipid,
protein, glucose and water-electrolyte. The symptoms include sodium retention, hypokalemia,
hypertension, moon face, bump back, diabetes, muscle wasting .
 Induction and aggravation of infection
 Possible risk of peptic ulcers
 Cardiovascular complications
Long-term use of GCS may cause hypertension and arteriolosclerosis
 Osteoporosis
GCS decrease bone density by multiple mechanisms, including inhibition of gonadal
steroid hormones, diminished gastrointestinal absorption of calcium and inhibition of bone
formation
 Other complications
Acute psychosis, hypomania , growth retardation and so on .

Withdrawl reactions
 Iatrogenic adrenocortical insufficiency : adrenocortical atrophy and adrenal
crisis
acute adrenal insufficiency results from too rapid withdrawl of GCS after prolonged
therapy, when the HPA axis has been suppressed.
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CRH
ACTH
GCS
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