Chapter 77: Adrenocortical Hormones
Guyton and Hall, Textbook of Medical Physiology, 12 edition
Adrenocortical Hormones
Fig. 77.1 Secretion of adrenocortical hormones by the different zones of
the adrenal cortex and secretion of catecholamines by the adrenal
medulla
Adrenocortical Hormones
• Adrenal Glands- lie at the superior poles of the
kidneys (suprarenal glands); each gland is
made up of a medulla and cortex
a. Adrenal medulla-makes up 20% of the gland and is
functionally related to the sympathetic nervous
system; secretes epinephrine and norepinephrine
b. Adrenal cortex-secretes the corticosteroids which
are synthesized from cholesterol
Adrenocortical Hormones
• Corticosteroids
a. Mineralocorticoids-especially affect the electrolytes
such as sodium and potassium
b. Glucocorticoids-exhibit important effects that
increase blood glucose concentrations
c. Androgenic hormones-exhibit the same effects as
testosterone
d. Over 30 isolated from the cortex but the two most
important are aldosterone and cortisol
Synthesis and Secretion of Adrenocorticoid Hormones
• Three Distinct Layers of the Adrenal Gland
a. Zona glomerulosa-thin layer just beneath the capsule;
secrete aldosterone; the secretion is controlled by
ECF concentrations of angiotensin II and potassium
b. Zona fasciculata-middle and widest layer; secretes the
glucocorticoids, cortisol and corticosterone as well as
small amounts of androgens; secretion is controlled
by ACTH
Synthesis and Secretion of Adrenocorticoid Hormones
• Three Distinct Layers of the Adrenal Gland
c. Zona reticularis-deepest layer of the cortex; secretes
the adrenal androgens DHEA, and androstenedione
as well as small amounts of estrogens; under the
control of ACTH
•
Adrenocortical Hormones are Steroids Derived
from Cholesterol
Fig. 77.2 Pathways for synthesis of steroid hormones by the adrenal cortex
Synthesis and Secretion of Adrenocortical Hormones
• Adrenocortical Hormones are Bound to Plasma
Proteins
• Adrenocortical Hormones are Metabolized in
the Liver
Functions of the Mineralocorticoids-Aldosterone
• Mineralocorticoid Deficiency Causes Severe Renal
Sodium Chloride Wasting and HyperkalemiaWithout mineralocorticoids, potassium ion
concentration ofo the ECF rises markedly,
sodium and chloride are rapidly lost from the
body, and the total ECF and blood volume
become greatly reduced
Functions of the Mineralocorticoids-Aldosterone
• Aldosterone is the Major Mineralocorticoid
a. 90% of the mineralocorticoid activity comes from
aldosterone and 10% comes from cortisol
b. Aldosterone increases renal tubular absorption of
sodium and the secretion potassium
c. Excess aldosterone increases ECF volume and
arterial pressure but has only a small effect on
plasma sodium concentration
Functions of the Mineralocorticoids-Aldosterone
Fig. 77.3 Effect of aldosterone infusion on arterial
pressure, ECF volume, and sodium
excretion in dogs
Functions of the Mineralocorticoids-Aldosterone
d. Excess aldosterone causes hypokalemia and
muscle weakness
e. Too little aldosterone causes hyperkalemia and
cardiac toxicity
f. Excess aldosterone increases tubular hydrogen
ion secretion and causes alkalosis
g. Aldosterone stimulates sodium and potassium
transport in sweat glands, salivary glands, and
intestinal epithelial cells
Functions of the Mineralocorticoids-Aldosterone
•
Cellular Mechanism of Aldosterone Action
a. Because of its lipid solubility, aldosterone
diffuses readily into the tubular epithelial
cell
b. It then combines with a receptor protein,
mineralocorticoid receptor
c. This complex or a product of the complex
diffuses into the nucleus eventually causing
DNA to form a mRNA
d. The mRNA diffuses back into the cytoplasm
where it induces protein synthesis
Functions of the Mineralocorticoids-Aldosterone
•
Cellular Mechanism of Aldosterone Action
e. The proteins formed are a mixture of (1) one
or more enzymes, and (2) membrane
transport proteins that all act together and
are required for sodium, potassium, and
hydrogen transport through the cell
membrane.
Functions of the Mineralocorticoids-Aldosterone
•
Cellular Mechanism of Aldosterone Action
Fig. 77.4
Functions of the Mineralocorticoids-Aldosterone
•
Nongenomic Actions of Aldosterone and
Other Steroid Hormones
a. Can increase the formation of cAMP in
smooth muscle cells and epithelial cells of
the renal collecting tubules
b. Can also stimulate the phosphatidylinositol
second messenger system
Functions of the Mineralocorticoids-Aldosterone
•
Regulation of Aldosterone Secretion
a. Increased K+ concentration in ECF greatly
increases aldosterone secretion
b. Increased angiotensin II in ECF greatly increases
aldosterone secretion
c. Increased Na+ concentration in the ECF very
slightly decreases aldosterone secretion
d. ACTH is necessary for aldosterone secretion but
has little effect in the rate of secretion in most
physiological conditions
Functions of the Mineralocorticoids-Aldosterone
•
Regulation of Aldosterone Secretion
Fig. 77.5 Effects of treating sodium depleted dogs with
an angiotensin converting enzyme (ACE)
inhibitor for 7 days to block formation of
angiotensin II and of infusing exogenous
angiotensin II to restore plasma
angiotensin II levels after ACE inhibition
Functions of the Glucocorticoids
•
Effects of Cortisol on Carbohydrate Metabolism
a. Stimulation of gluconeogenesis
1) Cortisol increases the enzymes required to
convert amino acids into glucose in the liver
cells
2) Cortisol causes mobilization of amino acids
from the extra-hepatic tissues (mainly from
muscle)
Functions of the Glucocorticoids
•
Effects of Cortisol on Carbohydrate Metabolism
b. Decreased glucose utilization by cells (moderate
decrease)
c. Elevated blood glucose concentration and
“adrenal diabetes” (when the blood sugar is 50%
greater than normal)
Functions of the Glucocorticoids
•
Effects of Cortisol on Protein Metabolism
a. Reduction in cellular protein (decreased synthesis
and increased catabolism)
b. Increase in liver and plasma proteins
c. Increased blood amino acids, diminished
transport of amino acids into extra-hepatic cells,
and enhanced transport into hepatic cells
Functions of the Glucocorticoids
•
Effects of Cortisol on Fat Metabolism
a. Increases the concentration of free fatty acids in
the plasma, increasing their utilization for energy
b. Obesity caused by excess cortisol (chest and head
region-”moon face”
Functions of the Glucocorticoids
•
Cortisol is Important in Resisting Stress and
Inflammation
a. Physical or neurogenic stress causes an immediate
increase in the secretion of ACTH, followed by an
increase in cortisol
Functions of the Glucocorticoids
•
Cortisol is Important in Resisting Stress and
Inflammation
Fig. 77.6 Rapid reaction of the adrenal cortex of a
rat to stress caused by fracture of the
tibia and fibula at time zero
Functions of the Glucocorticoids
•
Anti-Inflammatory Effects of High Levels of
Cortisol
a. Five main stages of inflammation:
1) Release of inflammatory chemicals from damaged
tissues and cells (i.e. histamine, prostaglandins,
leukotrienes, bradykinin, etc.)
2) Erythema-increased blood flow due to
vasodilation
3) Leakage of fluids leading to edema
4) Infiltration by leukocytes
5) Ingrowth of fibrous tissue in the healing process
Functions of the Glucocorticoids
•
Anti-Inflammatory Effects of High Levels of
Cortisol
b. Basic anti-inflammatory effects of cortisol
1) It can block the early stages of inflammation
before it actually begins
2) Causes rapid resolution of the inflammation and
increased rapidity of healing
Functions of the Glucocorticoids
•
Anti-Inflammatory Effects of High Levels of Cortisol
c. Cortisol prevents the development of inflammation by
stabilizing lysosomes and by other effects
1) Cortisol stabilizes the lysosomal membranes
2) Decreases the permeability of the capillaries
3) Decreases the migration of wbcs and
phagocytosis
4) Suppresses the immune system-decreasing
lymphocyte production
5) Attenuates fever (inhibits interleukin I production
Functions of the Glucocorticoids
•
Regulation of Cortisol Secretion by ACTH
a. ACTH stimulate cortisol secretion
b. ACTH secretion is controlled by corticotropin releasing
factor from the hypothalamus
c. ACTH activates adrenocortical cells to produce steroids
by increasing cAMP
Functions of the Glucocorticoids
•
Regulation of Cortisol Secretion by ACTH
Fig. 77.7 Mechanism for regulation of
glucocorticoid secretion, ACTH<
adrenocorticotropic hormone, CRF,
(corticotropin releasing factor)
Functions of the Glucocorticoids
•
Circadian Rhythm of Glucocorticoid Secretion
Fig. 77.8 Typical pattern of cortisol concentration
during the day.
Functions of the Glucocorticoids
•
Synthesis and Secretion of ACTH in Association with
Melanocyte-Stimulating Hormone, Lipotropin, and
Endorphin
Fig. 77.9
Functions of the Glucocorticoids
•
Abnormalities of Adrenocortical Secretion
a. Hypoadrenalism (Addison’s Disease)
b. Hyperadrenalism (Cushing’s Syndrome)