ADRENAL GLANDS
Division
HORMONES (type)
TRANSPORT, SYNTHESIS, AND METABOLISM
HYPOTHALAMUS
PITUITARY GLAND
TARGET GLAND
EFFECTS
Adrenal
Cortex
Glucocorticoid -
Cortisol (Steroid) in the
Zona Fasciculata
~80% LDL Cholesterol (also applies to other adrenal
cortex hormones)
1. Receptor-mediated endocytosis (LDLR)
2. Hydrolysis producing free cholesterol (FC)
3. Enters mitochondria via StAR protein
4. FC converted to pregnenolone via
CYP11A1/side chain convertase/desmolase
enzyme
Transport proteins:
1. 90% transcortin (CBG)
2. 7% albumin
3. 3% free
CRH (peptide) - produced by
paraventricular nucleus
Reaches APG via
hypophyseal portal vein then
binds to CRH-R1 in
corticotrophs to produce
ACTH
ACTH (peptide) - produced by
corticotropic cells and binds to
MC2R on adrenal cortex
GPCR → AC → PKA →
Exocytosis
Precursor: Proopiomelanocortin
Enzymes: PC1 and PC2
Products: ACTH, B-lipotropin,
N-terminal protein, Joining protein
ACTH has little effect on
aldosterone synthesis
Main regulator: Angiotensin II,
hyperkalemia
Cortisol
1. binds to glucocorticoid
hormone receptor (GR)
2. HSP90 will dissociate
3. GR enters nucleus
4. binds to DNA
5. transcription and protein
synthesis
Catabolic hormone
1. Increases glucose levels
- Inc. gluconeogenesis
- Dec. glycolysis
2. Mobilization of fats
3. Reduce inflammation by blocking
Phospholipase A2 (blocks prostaglandin and
eicosanoid synthesis)
4. Promotes lipolysis, bone resorption, and
muscle breakdown
Pulsatile release
1. Increased before and upon waking up to
prepare body for stressors
2. Lowest at night when asleep
Mineralocorticoid -
Aldosterone (Steroid)
in the Zona
glomerulosa
● Decreased 17-B-HSD activity
● Enhanced aldosterone synthase activity
● Transport proteins: 60% proteins leading to a
shorter half life than cortisol
Primarily regulates salt and extracellular volume
Increase sodium levels by increasing sodium
reabsorption in the kidneys
Promotes K+ secretion
Androgens (DHEA) in
the Zona reticularis
● Enhanced 17, 20 lyase activity
● Decreased 21-B hydroxylase activity (
● Enhanced DHEA sulfotransferase to produce
DHEAS (prolongs plasma half-life)
Transport proteins: SHBG (has low affinity to albumin
and globulins)
Converted to estrogen and testosterone
Androgens - No feedback
mechanism on CRH and ACTH
Adrenarche - increased adrenal androgen production
1-2 years before puberty
Adrenal
Medulla
Catecholamines:
Epinephrine (80%)
Norepinephrine (20%)
1. Tyrosine (from diet or phenylalanine) → DOPA
via tyrosine hydroxylase
2. DOPA → Dopamine via DOPA decarboxylase
3. Dopamine → NE via dopamine B-hydroxylase
4. NE → E via PNMT
5. Epinephrine is transported back to the granule for
storage
Pretty Tired Doctors Display No Emotion
Metabolism:
1. via COMT and MAO
2. Excreted as Vanillylmandelic acid (VMA) in the
urine
Transported into the chromaffin
granules by VMAT1
(catecholamine-H+ exchanger)
Receptors:
1. Alpha 1 - Gq - vasoconstriction, mydriasis,
bladder constriction
2. Alpha 2 - Gi - inhibits insulin secretion and
ACH and NE release
3. Beta 1 - increased HR (heart) and renin
release ( kidneys)
4. Beta 2 - bronchial smooth muscle dilation
(lungs)
5. Beta 3 - thermogenesis (adipocytes)
PATHOPHYSIOLOGY
Hormone Excess
1. Cushing’s syndrome - glucocorticoid (ACTH-secreting tumors, cortisol-secreting tumor, steroid intake)
a. Moon facies, buffalo hump, hyperglycemia, osteoporosis, recurrent infection
2. Androgen excess in women - Hirsutism, male pattern baldness, clitoral enlargement
3. Chronic steroid intake - mimics cortisol’s negative feedback mechanism = decreased ACTH and CRH
a. Leads to atrophy of zona fasciculata
b. Immediate stopping of steroid intake will lead to adrenal crisis = surge of ACTH and CRH release
4. Hyperaldosteronism - excess aldosterone (not severe due to counter regulatory mechanisms)
a. Hypernatremia
b. Counteracted by ADH
c. Increased ANP release - counteracts aldosterone and ADH
5. Pheochromocytoma - excess catecholamine
a. Chromaffin cell tumor
b. Hypertension, headaches, sweating, palpitations, chest pain
Hormone deficiency
1. Addison’s Disease - primary (adrenal gland defect)
a. Both aldosterone and cortisol are deficient
b. Aldosterone = Hypovolemia hypotension, hyperkalemia
c. Cortisol = weakness, anemia, ileus, hypoglycemia
d. Bronze pigmentation of the skin = due to increased MSH activity
2. Congenital adrenal hyperplasia (CAH)
a. Defect in 21B-OH
b. Low levels of aldosterone and cortisol
c. High levels of androgens
d. Inc. ACTH → hyperplasia → ambiguous genitalia
