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Steroid Hormones

The adrenal cortex is divided into 3 zones that synthesize various steroids from cholesterol & secrete them

Outer zona glomerulosa produces mineralocorticoids (for eg Aldosterone) which responsible for regulated primaryly by

renin-angiotensin sys

Middle zona fasciulata synthesis glucocorticoids (for eg Cortisol) which concerned with normal metabolism & resistance to

stress

Inner zona reticularis secrete adrenal androgenes

Secretion by 2 inner zones & to some extend, outer zone is controlled by pituitary (corticotropin, which is released in

response to hypothalamic coticotrophic releasing hormone. Glucocorticoid serve as feedback inhibitors of corticotropin &

corticotropin releasing factor secretion

Mechanism of action

The adenocorticoids binds to specific intracellular cytoplasmic receptors in target tissues

The receptor-hormone complex then translocates into nucleus where it acts as a transcription factor to turn genes on / off

depending on tissue

This mechanism requires time to produce an effect.

There are other glucocorticoid effects such as their requirement for catecholamine-mediated dilation of vascular & bronchial

musculature / lipolysis, whose effects are immediate

Glucocorticoids (GCs)

Short acting (t = 12 hours) : Hydrocortisone

Intermediate acting (t = 36 hours) : Prednizolon

Long acting (t = > 36 hours) : Triamcinolone, Betamethasone

They can use as therapeutic agents ina variety of disorders.

Major Pharmacokinetics of GCs

1. Promote normal & immediate metabolism

o GCs favor gluconeogenesis by both amino acid uptake by the liver & kidney , elevating activities of gluconeogenesis

enzymeso GCs stimulate protein catabolism (except in the liver) & lipolysis thereby providing the building blocks and

energy needed for glucose synthesis

2. resistance to stress

o By raising plasma glucose levels, GCs provide the body with the energy it requires to combat stress caused for eg. By

trauma, fright, infection, bleeding or debilitating disease

3. After blood cell levels in plasma

o GCs cause a in eosinophils , basophils , monocytes and lymphocytes

o In contrast, they the blood levels of Hb, RBC & platelets, polymorphonuclear leukocyte (important for treatment of

leukemia)

4. Antiinflammation action

o The most important therapeutic property of GCs is their ability to dramatically reduce the inflammation response & to

suppress immunity

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o The exact mechanism is complex & incompletely understood. However, it is known that the lowering & inhibition of

peripheral lymphocytes & macrophage play a role

o Also involved is the indirect inhibition of phospholipase A (due to the steroid mediated elevation of lipocortin ) ,which

blocks the release of arachidonic acid the precursor of the prostaglandin & leukotreines from membrane bound phospholipid

5. Affect other component of endocrine system

o Feedback inhibition of corticotrophin (ACTH) production , GCs cause inhibition of further glucocorticoid synthesis as well as

thyroid stimulating hormone production, whereas growth hormone production is

6. Effects on other systems

o There are mostly associated with the adverse effects on the hormones.

o High doses of GCs stimulate gastric acid & pepsin production & may exacerbate ulcers.o Effects on the CNS that influence mental status have been identified.o Chronic glucocorticoid therapy can cause severe bone loss.o Myopathy leads patients to complain of weakness

Therapeutic use of GCs

I. Replacement therapy for primary adrenocortical insufficiency (Addisons disease)

o This disease is caused by adrenal cortex dysfunction.o Hydrocortisone is given to correct the deficiency

II. Replacement therapy for secondary adrenocortical insufficiency

o The deficiency are caused by a defect either in CRF production by the hypothalamus or corticotrophin production by

pituitary.o Hydrocortisone is given

III. Diagnosis of Cushings syndrome

o This syndrome is caused by a hypersecretion of GCs that is due to either excessive release of corticotrophin by the anterior

pituitaty gland or to an adrenal tumor

o The Dexamethasone suppression test is used to diagnose the cause of individual case of Cushings syndrome.

o This synthetic glucocorticoid release by individual with pituitary dependent Cushings syndrome but it does not suppress

glucocorticoid release from adrenal gland

IV. Relief of inflammation symptoms

o GCs reduce the manifestation of inflammation. (eg. : rheumatoid & osteoarthritic inflammation, inflammation condition of

the skin ) including the redness, swelling, heat & tenderness that are commonly present in inflammatory site

V. Treatment of allergies

o GCs are useful in the treatment of the symptoms of drug, serum & transfusion allergic reaction, bronchial asthma & allergic

rhinitis.o Betanethasone. Triamanolone, Prednizolone are most effective

VI. Autoimmune disease

VII. Organs transplantation

VIII. Lymphatic leukemia

Adverse effects of GCsa. Osteoporosis

b. Peptic ulcerationc. Glucosuria ( hyperglycemia )

d. risk of infectione. appetitef. Hypertensiong. Edemah. Euphoria

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i. Psychoses

Mineralcorticoids

Desoxycorticosteronacetate (DOCA)

Fludrocortisone

AldosteroneThey have only mineralcorticoid activity :

renal excretion of Ca & K renal excretion of Na & HO

Adverse effects : Hypokalemia

Edema

Na retention (without hyperglycemia,osteoporosis, euphoria )

Fludrocortisone

A potent mineralcorticoid having someglucocorticoid activity as well, orally active usedfor :

a. replacement therapy of Addisons diseaseb. congenital adrenal hyperplasiac. idiopathic postural hypotension

GCs may be :o Orallyo InjecGon

o Inhalation

o Topica

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