Adrenocortical Hormones

P H Y S I O L O G Y
Dr. Jean Caringal • March 25, 2020
A.Y. 2019-2020 • 2nd Semester (Midterms)
Transcribers: Catalon, Castillo, Cespedes

OUTLINE

I. ADRENAL GLANDS I. ADRENAL GLANDS

A. CORTEX “Suprarenal Gland”
B. MEDULLA • Yellowish Retroperitoneal organs
C. BLOOD SUPPLY • Lie on the upper poles of each kidney
II. ADRENOCORTICAL HORMONES • Surrounded by Renal Fascia
A. ADRENOCORTICAL HORMONES ARE • Each gland has a yellow cortex and
STEROIDS DERIVED FROM • Dark brown medulla
CHOLOESTEROL
B. ADRENOCORTICAL HORMONES ARE
BOUND TO PLASMA PROTEIN
a. Cortisol
b. Aldosterone
C. ADRENOCORTICAL HORMONES ARE
METABOLIZED IN THE LIVER

III. FUNCTIONS OF MINERALOCORTICOIDS

A. ALDOSTERONE
a. Renal and circulatory effects of
aldosterone
b. Aldosterone stimulates sodium and
potassium transport in sweat glands, A. CORTEX -secretes hormones that include:
salivary glands, and intestinal epithelial a. Mineral corticoids, control of fluid and
cells electrolyte balance;
c. Cellular mechanism of aldosterone action b. Glucocorticoids, control of the metabolism of
d. Possible nongenomic actions of
aldosterone and other steroid hormones carbohydrates, fats, and proteins;
e. Regulation of aldosterone secretion c. Sex hormones (in small amounts), play a role in
the prepubertal development of the sex organs
IV. FUNCTIONS OF GLUCOCORTICOIDS

A. EFFECTS OF CORTISOL ON B. MEDULLA - secretes the catecholamines

CARBOHYDRATE METABOLISM a. Epinephrine
b. Norepinephrine
B. EFFECTS OF CORTISOL ON PROTEIN
METABOLISM
C. EFFECTS OF CORTISOL ON FAT
METABOLISM
D. IMPORTANCE OF CORTISOL IN
RESISTING STRESS AND INFLAMMATION
E. ANTI-INFLAMMATORY EFFECTS OF HIGH
LEVELS OF CORTISOL
V. REGULATION OF CORTISOL SECRETION BY
ACTH FROM THE PITUITARY GLAND
VI. ABNORMALITIES OF ADRENOCORTICAL
SECRETION
A. HYPOADRENALISM (ADRENAL
INSUFFICIENCY) – ADDISON’S DISEASE
B. HYPERADRENALISM—CUSHING’S
SYNDROME
C. PRIMARY ALDOSTERONISM (CONN’S
SYNDROME)
D. ADRENOGENITAL SYNDROME
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PHYSIOLOGY Adrenocortical Hormones

Right Suprarenal Left Suprarenal 4. release cholesterol that can be used to synthesize
Gland Gland adrenal steroid hormones
Pyramid shaped Crescentic in shape 5. Transport of cholesterol into the adrenal cells is
regulated by feedback mechanisms
Caps the upper pole of Extends along the 6. Cholesterols delivered to the mitochondria, where
the right kidney medial border of it is cleaved by the enzyme cholesterol desmolase
the left kidney to form PREGNENOLONE. (The rate-limiting step
from the upper in the eventual formation of adrenal steroids.)
pole of the hilus
B. ADRENOCORTICAL HORMONES ARE BOUND TO
Lies behind the right Lies behind the PLASMA PROTEIN
lobe of the liver and pancreas, the a. Cortisol
extends medially lesser sac, stomach • Approximately 90 to 95 % of the cortisol in
behind the inferior the plasma binds to plasma proteins: cortisol-
vena cava binding globulin or transcortin and lesser
extent, to albumin
Rests posteriorly on Rest posteriorly on • High degree of binding to plasma proteins
the diaphragm the diaphragm slows the elimination of cortisol from
the plasma  long half-life of 60 to 90
minutes.
C. BLOOD SUPPLY b. Aldosterone
a. Arteries • 60 % of circulating aldosterone bound with
Each gland are supported by three arteries: plasma proteins; 40 % is in the free form 
inferior phrenic artery, aorta and renal artery. relatively short half-life of about 20 minutes.
b. Veins IMPORTANCE OF BOUNDING
A single vein drains into the inferior vena cava • Serve as a reservoir to lessen rapid
on the right and into the renal vein on the left. fluctuations in free hormone concentrations.
c. Lymph Drainage • Help to ensure a relatively uniform
The lymph drains into the lateral aortic nodes. distribution of the adrenal hormones to the
d. Nerve Supply tissues.
Preganglionic sympathetic fibers derived from
the splanchnic nerves supply the glands. C. ADRENOCORTICAL HORMONES ARE METABOLIZED IN
THE LIVER
II. ADRENOCORTICAL HORMONES • Adrenal steroids are degraded mainly in the liver
and are conjugated to glucuronic acid and a lesser
A. ADRENOCORTICAL HORMONES ARE STEROIDS DERIVED extent to sulfates.
FROM CHOLESTEROL • Conjugated substances are inactive and do not
• Adrenal cortex can synthesize cholesterol from: have mineralocorticoid or glucocorticoid activity
 ACETATE  About 25% - excreted in the bile and then in
 LDL (80%) the feces
• Cholesterol synthesis of Adrenal Cortex:  Remaining conjugates - enter the
1. LDL diffuse from the plasma into the interstitial circulation unbound, and highly soluble in
fluid the plasma, thus filtered readily by the
2. LDL attach to specific receptors contained in kidneys and excreted in the urine
structures called coated pits on the adrenocortical Liver diseases - depress the rate of inactivation of
cell membranes. adrenocortical hormones.
3. coated pits are then internalized by endocytosis, Kidney diseases - reduce the excretion of the
forming vesicles that eventually fuse with cell inactive conjugates.
lysosomes

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PHYSIOLOGY Adrenocortical Hormones
III. FUNCTIONS OF MINERALOCORTICOIDS
A. ALDOSTERONE
• Mineralocorticoid Deficiency Severe Renal Sodium
Chloride Wasting and Hyperkalemia
 Without mineralocorticoids, potassium ion
concentration of the extracellular fluid
rises markedly, sodium and chloride are
rapidly lost from the body.
 Acute “lifesaving” portion
• Aldosterone Is the Major Mineralocorticoid
Secreted by the Adrenals
 Aldosterone exerts nearly 90 percent of
the mineralocorticoid activity of the
adrenocortical secretions
 Cortisol, the major glucocorticoid secreted
by the adrenal cortex, also provides a
significant amount of mineralocorticoid
activity.
a. RENAL AND CIRCULATORY EFFECTS OF
ALDOSTERONE
• Aldosterone increases renal tubular
reabsorption of sodium and secretion of
potassium.
• Excess aldosterone increases extracellular
fluid volume and arterial pressure but has
only a small effect on plasma sodium
concentration.
• Excess aldosterone causes hypokalemia
and muscle weakness; aldosterone
deficiency causes hyperkalemia and
cardiac toxicity.
• Excess aldosterone increases tubular
hydrogen ion secretion and causes
alkalosis.
b. ALDOSTERONE STIMULATES SODIUM AND
POTASSIUM TRANSPORT IN SWEAT GLANDS,
SALIVARY GLANDS, AND INTESTINAL EPITHELIAL
CELLS
• Sweat glands and Salivary glands
 These glands form a primary secretion that
contains large quantities of sodium
chloride
 Much of the sodium chloride, upon passing
through the excretory ducts, is reabsorbed,
whereas potassium and bicarbonate ions
are secreted.
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• Intestinal Epithelial Cells
 Aldosterone also greatly enhances sodium
absorption by the intestines, especially in
the colon, which prevents loss of sodium in
the stools.
c. CELLULAR MECHANISM OF ALDOSTERONE
ACTION
• Aldosterone diffuses readily to the interior
of the tubular epithelial cells.
• In the cytoplasm of the tubular cells,
aldosterone combines with a highly
specific cytoplasmic mineralocorticoid
receptor (MR) protein.
• Aldosterone-receptor complex or a
product of this complex diffuses into the
nucleus
• mRNA diffuses back into the cytoplasm,
where it causes protein formation.
d. POSSIBLE NONGENOMIC ACTIONS OF
ALDOSTERONE AND OTHER STEROID HORMONES.
• Aldosterone has been shown to increase
formation of cyclic adenosine monophosphate
(cAMP)
• Aldosterone has been shown to rapidly
stimulate the phosphatidylinositol second
messenger system.
e. REGULATION OF ALDOSTERONE SECRETION
4 factors are known to play essential roles in
regulation of aldosterone:
1. Increased potassium ion concentration in ECF =
Increased aldosterone secretion.
2. Increased angiotensin II concentration in ECF =
Increased aldosterone secretion.
3. Increased sodium ion concentration in the eCF =
slightly decreased aldosterone secretion.
4. ACTH from the anterior pituitary gland is
necessary for aldosterone secretion but has
little effect in controlling the rate of secretion in
most physiological conditions
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PHYSIOLOGY Adrenocortical Hormones

IV. FUNCTIONS OF GLUCOCORTICOIDS

A. EFECTS OF CORTISOL ON CARBOHYDRATE

METABOLISM

• Stimulation of gluconeogenesis
1. Cortisol increases the enzymes required to
convert amino acids into glucose in liver cells
2. Cortisol causes mobilization of amino acids from
the extrahepatic tissues, mainly from muscle.
3. Cortisol antagonizes insulin’s effects to inhibit
gluconeogenesis in the liver.
• Decrease glucose utilization of cells
• Elevated blood glucose concentration and “Adrenal
Diabetes”
REGULATION OF ALDOSTERONE SECRETION
B. EFFECTS OF CORTISOL ON PROTEIN METABOLISM

• Reduction in Cellular protein

 Reduction is caused by both decreased synthesis
and increased catabolism of protein already in
the cells. Also it may be from decreased amino
acid transport into extrahepatic tissues
• Cortisol Increases Liver and Plasma Proteins
 All proteins in the body is affected except in the
liver
 Because of the exception, plasma protein
production is increased

Renin-angiotensin-aldosterone system (RAAS) - is a

vital system of human body, as it maintains plasma C. EFFECTS OF CORTISOL ON FAT METABOLISM
sodium concentration, arterial blood pressure and • Mobilization of fatty acids from adipose tissue
extracellular volume. Kidney-secreted renin enzyme
• Excess cortisol causes obesity
acts on its substrate to form angiotensin II, a versatile
effector peptide hormone.
D. IMPORTANCE OF CORTISOL IN RESISTING STRESS AND
RENIN- produced by juxtaglomerular apparatus of the INFLAMMATION
kidney. Rate-limiting step in RAA sytem. Increased in:
Controlled by 4 factors: • Trauma
• NaCl by the macula densa cells • Surgery
• Renal arterial pressure • Infection
• Sympathetic NS- in response to • Injection of necrotizing substances
upright posture • Intense heat or cold
• Humoral: potassium, angiotensin II, • Restraining an animal so it cannot move
ANP • Injection of norepinephrine
Aldosterone- controlled by 3 primary factors: • Debilitating disease
• Angiotensin II, Potassium, ACTH • And other symphathomimetic drugs
NOTE: Extracellular Volume – IN, Potassium- OUT

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PHYSIOLOGY Adrenocortical Hormones

E. ANTI-INFLAMMATORY EFFECTS OF HIGH LEVELS OF

CORTISOL
• Cortisol prevents the development of
Inflammation by:
 Stabilization of lysosomal membranes.
 Decreasing permeability of the capillaries
 Decreasing both migration of white blood cells
into the inflamed area and phagocytosis of the
damaged cells
 Suppressing the immune system, causing
lymphocyte production to decrease markedly
 Attenuating fever mainly because it reduces
release of interleukin-1 from white blood cells

• Other effects of cortisol

 Cortisol blocks the inflammatory response to
allergic reactions.
 Effect on blood cells and on immunity in
infectious diseases.
 Cortisol decreases number of eosinophils and
• Cortisol has direct negative feedback effects
lymphocytes in the blood.
1. Hypothalamus to decrease the formation of CRF.
 Large doses of cortisol causes significant atrophy
2. Anterior pituitary gland to decrease the formation of
of lymphoid tissue throughout the body, which
ACTH.
in turn decreases the output of T cells and
 The secretory rates of CRF, ACTH, and cortisol are
antibodies from the lymphoid tissue, leading to
high in the early morning but low in the late
low immunity for almost all foreign invaders of
evening.
the body.
 Pro-opiomelanocortin (POMC)- a preprohormone
which is the precursor of ACTH and several other
V. REGULATION OF CORTISOL SECRETION BY ACTH
peptides : melanocyte-stimulating hormone (MSH),
FROM THE PITUITARY GLAND
β-lipotropin, β-endorphin, and a few others.

Hypothalamus Regulation of Cortisol

Anterior Pituitary Gland • Cortisol when released into the bloodstream is

Adrenals
(Activation of Adenyl Cyclase)
Activation of Protein Kinase A
bound to plasma protein- CORTISOL BINDING
PROTEIN (CBG) and to a small extent
ALBUMIN.
• It has a short half life (60-90 minutes). Most of
the cortisol produced are metabolized by the
liver.

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PHYSIOLOGY Adrenocortical Hormones
Glucocorticoids (S) exert their effect by entering the
cell by passive diffusion (since they very lipid soluble).
Once inside the cell, (S) is joined by a chaperone
molecule (HSP- Heat shock protein) until it meets the
receptor (R). Before binding with the (R), (S) will
dissociate from the HSP. The activation of the
receptor leads to alteration of DNA transcription and
translation leading to response glucocorticoids.
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Effects of Cotisol
1. Gluconeogenesis and glycogen synthesis (in
fasting state)
• Inhibition of glucose uptake by the
muscles
• Increased lipolysis
• Summative effect: Increased serum
glucose
2. Thinning of the skin
3. Osteoporosis
• Due to increased osteoclast activity
(bone resorption)
4. Decreased function and distribution of the
leukocytes (WBC); decreased chemokine and
cytokine production
• Inhibition of phospholipase A2 (the
enzyme that converts cholesterol to
arachidonic acid- the source of
prostaglandins)
5. Increased RBC and platelet count
6. In the central nervous system: Insomnia,
Depression
7. Increased incidence of gastric mucosal ulcer
8. Increased fetal lung surfactant
VI. ABNORMALITIES OF ADRENOCORTICAL SECRETION
A. HYPOADRENALISM (ADRENAL INSUFFICIENCY) –
ADDISON’S DISEASE
• Adrenal cortices are unable to produce sufficient
adrenocortical hormones
• Most frequently caused by primary atrophy (80 %
of cases is due to autoimmunity) or injury
Characteristics:
 Mineralocorticoid Deficiency
 Glucocorticoid Deficiency
 Melanin Pigmentation
 Addisonian Crisis - critical need for extra
glucocorticoids and the associated severe
debility in times of stress.
B. HYPERADRENALISM—CUSHING’S SYNDROME
• Most commonly caused by excess ACTH secretion
Hypercortisolism:
(1) Adenomas of the anterior pituitary
(2) Abnormal function of the hypothalamus
(3) Ectopic secretion of ACTH by a tumor
(4) Adenomas of the adrenal cortex
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PHYSIOLOGY Adrenocortical Hormones

• Large doses of dexamethasone- used to distinguish APPENDIX

between ACTH dependent and ACTH-independent
Cushing’s syndrome
Characterized by:
Mobilization of fat from the lower part of the body 
buffalo-like torso

• Edematous appearance of the face- moon face

• Acne & Hirsutism
• Hypertension
• Enhanced gluconeogenesis and decreased glucose
utilization
C. PRIMARY ALDOSTERONISM (CONN’S SYNDROME)
• A small tumor of the zona glomerulosa cells occurs
and secretes large amounts of aldosterone
• Hyperplastic adrenal cortices secrete aldosterone
rather than cortisol
• Hypokalemia, mild metabolic alkalosis, a slight
increase in extracellular fluid volume and blood
volume, a modest increase in plasma sodium
concentration and hypertension.
• Decreased plasma renin concentration
ADRENOGENITAL SYNDROME
D. ADRENOGENITAL SYNDROME
• Adrenocortical tumor secretes excessive quantities
of androgens  intense masculinizing effects

In females:
• Growth of a beard
• A much deeper voice
• Occasional baldness if she also has the genetic trait
for baldness
• Masculine distribution of hair on the body and the
pubis
• Growth of the clitoris to resemble a penis
• Deposition of proteins in the skin and especially in
the muscles.

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PHYSIOLOGY Adrenocortical Hormones

References:
Doc Jean Caringal PPT (Black font)
Plenary 1 PPT
Medical Physiology by Guyton and Hall 13th ed.

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