Endocrine Physiology

The Adrenal Gland 1

Dr.absar ullah khan

 Adrenal (Suprarenal) Glands
Cortex
• Adrenal glands are paired, Medulla
pyramid-shaped organs at the
top of the kidneys.
• Weigh 6-10 g.
• Structurally and functionally, they are two
glands in one
• Adrenal cortex (80-90%)– glandular
tissue derived from embryonic mesoderm
• Adrenal medulla (10-20%)– formed from
neural ectoderm, can be considered a
modified sympathetic ganglion
 Adrenal Cortex
• Synthesizes and releases steroid hormones
(corticosteroids)
• Different corticosteroids are produced in each of
the three layers:
• Zona glomerulosa – mineralocorticoids
(mainly aldosterone)
• Zona fasciculata – glucocorticoids
+Androgens
(mainly cortisol and corticosterone)
• Zona reticularis – gonadocorticoids +
glucocorticoids
(mainly dehydroepiandrosterone DHEA)
 Adrenal Gland

Guyton and Hall

 Adrenal Cortex

Salt

Sugar

Sex

Guyton and Hall

 HPA Axis

Guyton and Hall

 Steroid Hormones: Structure

Guyton and Hall

 Steroid Hormones Synthesis

• Steroids are derivatives of cholesterol

• Cholesterol is from the lipid droplets

in cortical cells
• Removed cholesterol is replenished by cholesterol
in LDL in blood or synthesized from acetate

- LDL is a complex composed of

cholesterol, phospholipids,
triglycerides, and proteins
(proteins and phospholipids make
LDL soluble in blood).
- LDL is taken into cells
via LDL receptors, and broken
down into esterified cholesterol,
and then free cholesterol:
Steroid Hormones Synthesis (Cont.)

• Steroid hormones are synthesized and secreted on

demand (not stored)
• The first and rate-limiting step in the synthesis of
all steroid hormones is conversion of cholesterol
to pregnenolone by the enzyme cholesterol
dismolase (cholesterol side chain cleavage
enzyme (SCC))
• Newly synthesized steroid hormones are rapidly
secreted from the cell
• Following secretion, all steroids bind to some
extent to plasma proteins: CBG (corticosteroid
binding globulin) and albumin
Steroidogenesis: Steroidogenesis entails processes by which cholesterol is converted to
biologically active steroid hormones
 Genetic Defects in Adrenal Steroidogenesis
• Congenital adrenal hyperplasias: Congenital adrenal
hyperplasia (CAH) are any of several autosomal recessive diseases resulting
from mutations of genes for enzymes mediating the biochemical steps of production
of cortisol from cholesterol by the adrenal glands (steroidogenesis).

cortisol ACTH ِAdrenal hyperplasia

 Congenital adrenal hyperplasias

• 21-hydroxylase (P450c21) deficiency:

cortisol, corticosterone, and aldosterone
deficiency
*ACTH Adrenal hypertrophy and high
amounts of androgen

* Virilization of female (masculanization)

Steroid Hormones: Action

Guyton and Hall

Hormones of adrenal cortex
production concentr. activity activity
mg/day ng/ml MINERAL. GLUCO.

aldosterone 0.05-0.15 0.15 90%

deoxycorti- 0.6 0.15 1/15

costerone

corticoste- 1-4 2-4 1/50 4%

rone
cortisol 8-25 40-180 1/400 95%

DHEA 7-15 5
1- Cortisol is at 1000 fold higher
concentrations than aldosterone
2- Corticosterone >>>>aldosterone
3- Cortisol binds well to the mineralocorticoid
receptor
Mineralocorticoids: Aldosterone

• A steroid hormone.
• Essential for life.
• Synthesized in zona glomerulosa
• Responsible for regulating Na+ reabsorption in
the distal tubule and the cortical collecting duct
• Target cells are called “principal (P) cell”.
• It also affects Na+ reabsorption by sweat,
salivary and intestinal cells.
* Stimulates synthesis of more Na/K-ATPase pumps.
Mineralocorticoids: Aldosterone

• Aldosterone secretion is stimulated by:

• Decreasing blood volume or pressure (renin-
angiotensin system).
• Rising blood levels of K+
• Low blood Na+
• ACTH
 Aldosterone synthesis

• Voltage-sensitive calcium channels open and the intracellular calcium

concentration increases—activating calcium calmodulin kinase.
• Calcium channel blockers inhibit aldosterone synthesis.
• Aldosterone levels fluctuate diurnally—
highest concentration being at 8 AM, lowest
at 11 PM, in parallel to cortisol rhythms.
The Four Mechanisms of Aldosterone Secretion

• Renin-angiotensin mechanism – kidneys release

renin, which stimulates angiotensin II that in
turn stimulates aldosterone release
• Plasma concentration of potassium and sodium–
directly influences the zona glomerulosa cells
• ACTH – causes small increases of aldosterone
during stress
• Atrial natriuretic peptide (ANP) – inhibits activity
of the zona glomerulosa
 The Four Mechanisms of Aldosterone Secretion

Guyton and Hall

 Actions of Aldosterone

Stimulates sodium reabsorption by distal tubule

and collecting duct of the nephron and
promotes potassium and hydrogen ion excretion
• Increases transcription of Na/K pump
• Increases the expression of apical Na channels
and an Na/K/Cl cotransporter

• Expands ECF volume

• Aldosterone binds to the mineralocorticoid receptor in
target cells and affects transcriptional changes typical of
steroid hormone action.
• The kidney is the major site of mineralocorticoid activity.
 Aldosterone: Role in diseases

• Complete failure to secrete aldosterone leads to

death (dehydration, low blood volume).

• Hyperaldosterone states: Contribute to

hypertension associated with increased blood
volume.
 Overproduction of aldosterone

• primary causes, ie. Conn’s syndrome

• adenoma, nodular hyperplasia of zona
glomerulosa
• secondary
• cirrhosis, ascites, nephrotic syndrome
• symptoms, signs
• headache, hypokalemia causing muscle
weakness, hypernatremia, hypervolemia,
nocturnal polyuria, hand cramping
Overproduction of aldosterone

• treatment
• surgical for adenoma
• Spironolactone