2. The glucocorticoids (cortisol, corticosterone)
are primarily involved in the control of glucose
metabolism and the body’s ability to deal with
stress.
Mineralocorticoids, such as aldosterone, are
involved in maintaining fluid and electrolyte
balance in the body.
3. Role of Glucocorticoids
in Normal Function
The primary glucocorticoid released in humans is
cortisol (also known as hydrocortisone).
4. Mechanism of Action
of Glucocorticoids
Specifically, glucocorticoids exert their classic
cellular effects first by entering the target cell
and binding to a receptor located in the cytosol.
Binding the glucocorticoid to the receptor
creates an activated hormone-receptor complex.
This activated complex then travels
(translocates) to the nucleus of the cell, where it
binds directly to specific DNA gene segments
that control inflammation.
6. Anti-Inflammatory Effects
glucocorticoids often inhibit transcription
factors that normally stimulate genes within
specific cells to express inflammatory
components.
Glucocorticoids—for example—act on
macrophages, lymphocytes, and endothelial
cells to inhibit the expression of inflammatory
proteins (cytokines) such as interleukin-1,
interleukin-6, tissue necrosis factor alpha,
interferon gamma, and similar inflammatory
cytokines.
7. Immunosuppression
Glucocorticoids have long been recognized
for their ability to inhibit hypersensitivity
reactions, especially delayed or cell-mediated
allergic reactions.
Many immunosuppressive effects are
mediated by the same actions that explain the
anti inflammatory effects of these drugs.
9. Glucocorticoid Use in Endocrine
Conditions
Replacement Therapy
Glucocorticoid replacement is instituted in
both primary and secondary adrenal
insufficiency.
In primary insufficiency (Addison disease),
glucocorticoid production is deficient because
of the destruction of the adrenal cortex.
In secondary insufficiency, adrenal cortex
function is diminished because of other
factors, such as a lack of adequate ACTH
release from the anterior pituitary.
Replacement therapy can also be initiated
12. Adverse Effects of
Glucocorticoids
Adrenocortical Suppression
Drug-Induced Cushing Syndrome
(adrenocortical hypersecretion)
Breakdown of Supporting Tissues
Other Adverse Effects
o Peptic ulcer
o Glaucoma
o psychoses
14. Mineralocorticoids
Mineralocorticoids are also steroid
hormones that are produced by the
adrenal cortex.
The principal mineralocorticoid in
humans is aldosterone.
Aldosterone is primarily involved in
maintaining fluid and electrolyte balance
in the body.
This hormone works on the kidneys to
increase sodium and water reabsorption
15. Regulation of Mineralocorticoid
Secretion
A primary stimulus for aldosterone release is increased
levels of angiotensin II
Basically, a sudden fall in blood pressure initiates a chain
of events that generates increased circulating levels of
angiotensin II
Angiotensin II helps maintain blood pressure by
vasoconstricting peripheral vessels
Angiotensin II helps exert a more prolonged
antihypotensive effect by stimulating aldosterone
secretion from the adrenal cortex.
In addition, aldosterone secretion is regulated by
increased plasma potassium levels
Elevated plasma potassium serves as a stimulus to
(1) Aldosterone (A) enters the cell and binds to a cytosolic receptor (R), creating an activated hormone-receptor complex (A–R). (2) A–R complex travels to the cell’s nucleus, where it induces mRNA synthesis. (3) mRNA units undergo translation in the cytosol. (4) Specific proteins are synthesized that increase membrane permeability to sodium (Na). (5) Na leaves the nephron lumen and enters the cell down an electrochemical gradient. (6) Na is actively reabsorbed into the body, and potassium (K) is actively secreted from the bloodstream by the cellular Na-K pump.
