3. ZONA GLOMERULOSA
OVERVIEW
‣ The Adrenal glands are paired endocrine glands found on top of the kidneys
‣ They are composed of an inner medulla and an outer cortex, which is in turn
divided into three zones
‣ The zona glomerulosa is the outermost layer of the adrenal cortex
‣ It is responsible for secreting the mineralocorticoid hormones which are
important in regulating fluid balance
‣ Learning Goal
‣ To discuss the structure of the zona glomerulosa, as well as the functions
of the hormones it produces
4. ZONA GLOMERULOSA
STRUCTURE
‣ The zona glomerulosa is the outermost layer of the adrenal cortex, lying
just below the fibrous adrenal capsule
‣ It accounts for around 15% of the thickness of the cortex
‣ The secretory cells of the zona glomerulosa are arranged in oval-
shaped clusters
‣ its name comes from the latin word “glomus” (meaning ball)
‣ These clusters are divided by connective tissue bands called trabeculae
which extend down into the cortex from the adrenal capsule
‣ The blood supply to the secretory cells travels within these trabeculae
6. ZONA GLOMERULOSA
FUNCTION
‣ The primary function of the zona glomerulosa is the synthesis
of mineralocorticoid hormones, which play an important role in the
maintenance of electrolyte and water balance in the body
‣ Mineralocorticoids are steroid hormones, and so are synthesized
from cholesterol
‣ The most important mineralocorticoid is aldosterone, which is responsible
for controlling the uptake of Na+ and secretion of K+ in the collecting duct
of the renal tubule
‣ Aldosterone acts within the tubule cell to increase the transcription of Na+/
K+-ATPase and ENaC (epithelial sodium channels), promoting re-absorption
of Na+ and excretion of K+
8. ZONA GLOMERULOSA
FUNCTION
‣ The following factors increase the rate of aldosterone production within the zona glomerulosa:
‣ Increase in plasma concentration of Angiotensin-II
‣ Increase in plasma K+ concentration
‣ Decrease in plasma pH (acidosis)
‣ Decreased blood pressure, as detected by atrial stretch receptors
‣ It is also worth noting that aldosterone secretion follows a diurnal rhythm, with higher levels
typically being released during sleep
‣ While all the previous factors are important in the production and secretion of aldosterone,
one of the most important is the plasma concentration of Angiotensin-II
‣ The release of aldosterone is therefore an important part of the renin-angiotensin-aldosterone
system (RAAS) which is fundamental in the long-term regulation of blood pressure
14. ZONA GLOMERULOSA
REVIEW QUESTIONS
‣ Which of the following best describes the primary function
of the Zona Glomerulosa?
‣ Breakdown of aldosterone
‣ Synthesis of testosterone
‣ Synthesis of mineralocorticoids
‣ Storage of adrenaline
15. ZONA GLOMERULOSA
REVIEW QUESTIONS
‣ Which of the following best describes the primary function
of the Zona Glomerulosa?
‣ Breakdown of aldosterone
‣ Synthesis of testosterone
‣ Synthesis of mineralocorticoids
‣ Storage of adrenaline
16. ZONA GLOMERULOSA
REVIEW QUESTIONS
‣ The Zona Glomerulosa's role is to synthesize
mineralocorticoids. These are steroid hormones that
regulate electrolyte and water balance within the body.
17. ZONA GLOMERULOSA
REVIEW QUESTIONS
‣ Which of the following would produce an increase in the
rate of aldosterone production?
‣ Increase in plasma pH (becomes more alkaline)
‣ Decrease in potassium ion concentation
‣ Increase in plasma Angiotensin-II
‣ All of the above
18. ZONA GLOMERULOSA
REVIEW QUESTIONS
‣ Which of the following would produce an increase in the
rate of aldosterone production?
‣ Increase in plasma pH (becomes more alkaline)
‣ Decrease in potassium ion concentation
‣ Increase in plasma Angiotensin-II
‣ All of the above
21. ZONA GLOMERULOSA
REVIEW QUESTIONS
‣ Conn's syndrome is characterised by excess aldosterone
release, usually from an adenoma in the Zona
Glomerulosa
23. ZONA FASCICULATA
OVERVIEW
‣ The Zona Fasciculata is the middle zone of the Adrenal
Cortex, deep to the Zona Glomerulosa and superficial to
the Zona Reticularis
‣ It is the thickest of the three Zonas, measuring approximately
0.9mm and making up 50% of the mass of the Adrenal Gland
‣ Learning Goal
‣ To discuss the cellular arrangement, function and clinical
relevance of the Zona Fasciculata
24. ZONA FASCICULATA
STRUCTURE
‣ The Zona Fasciculata is made up of parenchymal cells
known as spongiocytes, arranged into columns (sometimes
called fascicles) with venous sinuses in between
‣ Blood flows into the adrenal gland from the adrenal
arteries, which are branches of the phrenic and renal
arteries as well as the aorta
‣ From here, blood flows through the adrenal tissue from
superficial to deep, draining into sinusoids in the adrenal
medulla and eventually into the central adrenal vein
26. ZONA FASCICULATA
FUNCTION
‣ The cells of the Zona Fasciculata secrete the
glucocorticoids Cortisol and Corticosterone
‣ These hormones regulate carbohydrate metabolism,
particularly when an individual is in a time of stress (as part
of the “fight-or-flight” response)
‣ In an adult human, approximately 10mg of Cortisol and
3mg of Corticosterone are secreted over a 24-hour period
28. ZONA FASCICULATA
FUNCTION
‣ The synthesis pathway of the steroids secreted by the Zonas of
the adrenal gland is complex
‣ Cholesterol is the major precursor for all steroids secreted
‣ The first step is initiated by the actions of ACTH and
Angiotensin II activating adenylyl cyclase and phospholipase
C respectively
‣ Cholesterol can then be converted to a steroid called
Pregnenolone via an enzyme of the cytochrome P450
superfamily called cholesterol desmolase
29. ZONA FASCICULATA
FUNCTION
‣ From Pregnenolone, all the major secreted
mineralocorticoids, glucocorticoids and androgens can be
synthesized in a multi-step enzyme-assisted pathway
‣ The metabolites of the synthesis pathway are moved in
and out of the mitochondria, the smooth endoplasmic
reticulum and the cytoplasm
30. ZONA FASCICULATA
FUNCTION
‣ It is the presence or lack of specific enzymes in each Zona
that determines which hormones are secreted
‣ In the Zona Fasciculata, the enzyme 11β-hydroxylase
catalyses the final step of the reaction that forms Cortisol
and Corticosterone
‣ Additionally the secretion of cortisol follows a diurnal
pattern with more being secreted in the mornings
41. ZONA FASCICULATA
REVIEW QUESTIONS
‣ Approximately how much cortisol is released from an
adult’s Zona Fasciculata over 24 hours?
‣ 0.1mg
‣ 1mg
‣ 10mg
‣ 100mg
42. ZONA FASCICULATA
REVIEW QUESTIONS
‣ Approximately how much cortisol is released from an
adult’s Zona Fasciculata over 24 hours?
‣ 0.1mg
‣ 1mg
‣ 10mg
‣ 100mg
44. ZONA FASCICULATA
REVIEW QUESTIONS
‣ Which enzyme catalyses the final step on the synthesis
pathway for cortisol?
‣ 3β-hydroxysteroid dehydrogenase
‣ 11β-hydroxylase
‣ 21β-hydroxylase
‣ 17,20-lyase
45. ZONA FASCICULATA
REVIEW QUESTIONS
‣ Which enzyme catalyses the final step on the synthesis
pathway for cortisol?
‣ 3β-hydroxysteroid dehydrogenase
‣ 11β-hydroxylase
‣ 21β-hydroxylase
‣ 17,20-lyase
46. ZONA FASCICULATA
REVIEW QUESTIONS
‣ Options 1,3 and 4 are all enzymes involved in the pathway
of synthesising steroids from cholesterol, but it is option 2
that is part of the final step in cortisol synthesis.
47. ZONA FASCICULATA
REVIEW QUESTIONS
‣ Which of the following is NOT a common symptom of
Cushings syndrome?
‣ "Salt and Pepper" sign
‣ "Buffalo hump" sign
‣ Irregular menstrual periods
‣ Thinning of skin
48. ZONA FASCICULATA
REVIEW QUESTIONS
‣ Which of the following is NOT a common symptom of
Cushings syndrome?
‣ "Salt and Pepper" sign
‣ "Buffalo hump" sign
‣ Irregular menstrual periods
‣ Thinning of skin
49. ZONA FASCICULATA
REVIEW QUESTIONS
‣ "Salt and Pepper" sign is seen on radiographs in those
with parathyroid issues. Visit our page on The Parathyroid
Gland for more information.
51. ZONA RETICULARIS
OVERVIEW
‣ The Zona Reticularis is the innermost layer of the adrenal
cortex, it is deep to the Zona Glomerulosa and the Zona
Fasciculata and superficial to the Adrenal Medulla
‣ It is responsible for production and secretion of androgens
‣ Learning Goal
‣ To discuss the cellular arrangement, function and
clinical relevance of the Zona Reticularis
52. ZONA RETICULARIS
STRUCTURE
‣ The zona reticularis is composed of cylindrical masses of
epithelia arranged in an irregular, net-like pattern
‣ In comparison to the zona fasciculata, the cells contain
fewer vacuoles and appear more irregular and smaller in
size
54. ZONA RETICULARIS
FUNCTION
‣ The zona reticularis is the site of biosynthesis of androgen precursors
such as dehydroepiandrosterone (DHEA) and androstenedione from
cholesterol
‣ These androgens are released into the bloodstream and transported
to gonads where they are converted into testosterone or oestrogen
‣ These are largely responsible for the normal development
of sexual characteristics during puberty
‣ In postmenopausal women, the conversion of adrenal androgens to
oestrogen is the only source of oestrogen synthesis and hence is a
significant source
56. ZONA RETICULARIS
REGULATION OF ADRENAL ANDROGENS
‣ Adrenal androgens are regulated by ACTH (adrenocorticotropic
hormone) secreted from the anterior pituitary gland which is
stimulated by the release of CRH (corticotrophin releasing
hormone) from the hypothalamus
‣ However, the adrenal androgens along with their potent
metabolites such as testosterone do not negatively feedback to
ACTH or CRH
‣ Therefore, in cases where there is a dramatic increase in ACTH,
this leads to excess production of androgens which cannot be
regulated
59. ZONA RETICULARIS
REVIEW QUESTIONS
‣ Which layers of the adrenal gland book-end the Zona
Reticularis?
‣ Zona Fasiculata & Zona Glomerulosa
‣ Zona Glomerulosa & Medulla
‣ Zona Fasiculata & Medulla
‣ Zona Fasiculata & Cortex
60. ZONA RETICULARIS
REVIEW QUESTIONS
‣ Which layers of the adrenal gland book-end the Zona
Reticularis?
‣ Zona Fasiculata & Zona Glomerulosa
‣ Zona Glomerulosa & Medulla
‣ Zona Fasiculata & Medulla
‣ Zona Fasiculata & Cortex
61. ZONA RETICULARIS
REVIEW QUESTIONS
‣ Zona Glomerulosa is the most superficial layer, then Zona
Fasiculata, then Zona Reticularis, then Medulla is the
deepest. The Cortex is made up of the Zonas Glomerulosa,
Fasiculata and Reticularis together.
62. ZONA RETICULARIS
REVIEW QUESTIONS
‣ What is the primary function of the Zona Reticularis?
‣ Storage of androgens
‣ Synthesis of androgens
‣ Breakdown of androgens
‣ Synthesis of mineralocorticoids
63. ZONA RETICULARIS
REVIEW QUESTIONS
‣ What is the primary function of the Zona Reticularis?
‣ Storage of androgens
‣ Synthesis of androgens
‣ Breakdown of androgens
‣ Synthesis of mineralocorticoids
‣ Androgens such as DHEA are synthesized in the Zona
Reticularis
64. ZONA RETICULARIS
REVIEW QUESTIONS
‣ Where are androgens such as DHEA converted to
testosterone and oestrogen?
‣ Adrenal Medulla
‣ Liver
‣ Kidney
‣ Gonads
65. ZONA RETICULARIS
REVIEW QUESTIONS
‣ Where are androgens such as DHEA converted to
testosterone and oestrogen?
‣ Adrenal Medulla
‣ Liver
‣ Kidney
‣ Gonads
66. ZONA RETICULARIS
REVIEW QUESTIONS
‣ DHEA and other androgen "precursors" are released into
the bloodstream and converted into testosterone/
oestrogen in the testes/ovaries respectively. Androgen
levels are higher in males than females.
67. ZONA RETICULARIS
REVIEW QUESTIONS
‣ What kind of genetic inheritance pattern is demonstrated
by Congenital Adrenal Hyperplasia?
‣ Autosomal dominant
‣ Autosomal recessive
‣ X-linked
‣ Y-linked
68. ZONA RETICULARIS
REVIEW QUESTIONS
‣ What kind of genetic inheritance pattern is demonstrated by
Congenital Adrenal Hyperplasia?
‣ Autosomal dominant
‣ Autosomal recessive
‣ X-linked
‣ Y-linked
‣ Most common are enzyme deficiencies that follow an
autosomal recessive pattern.
69. ZONA RETICULARIS
REVIEW QUESTIONS
‣ Which of the following is a common feature of congenital
adrenal hyperplasia?
‣ Excess testosterone
‣ Insufficient testosterone
‣ Insufficient oestrogen
‣ Excess mineralocorticoid
70. ZONA RETICULARIS
REVIEW QUESTIONS
‣ Which of the following is a common feature of congenital
adrenal hyperplasia?
‣ Excess testosterone
‣ Insufficient testosterone
‣ Insufficient oestrogen
‣ Excess mineralocorticoid
‣ CAH is characterized by low mineralocorticoid and excess
testosterone and its derivatives
72. ADRENAL MEDULLA
OVERVIEW
‣ The adrenal medulla is the central part of the adrenal
gland, surrounded by the cortex
‣ The medulla plays a very important role in homeostasis: it
serves to secrete adrenaline and noradrenaline
‣ Learning Goal:
‣ To cover the structure, function and clinical relevance
of the adrenal medulla
73. ADRENAL MEDULLA
STRUCTURE
‣ The adrenal glands, also known as supra-renal glands, are found immediately
superior to the kidneys
‣ They are retroperitoneal structures and composed of two major regions: the outer
adrenal cortex and the inner adrenal medulla
‣ The main secreting cells of the adrenal medulla are called chromaffin cells, which
are neuroendocrine cells that are modified sympathetic ganglia
‣ The chromaffin cells are neural crest cell derivatives
‣ Adrenaline is released in response to activation of the sympathetic nervous system
‣ (fibres of which are carried to the adrenal medulla by the thoracic splanchnic
nerves)
75. ADRENAL MEDULLA
FUNCTION
‣ The adrenal medulla is mainly responsible for the
synthesis of the catecholamines, adrenaline and
noradrenaline, but also has other secretory functions such
as the production of dopamine
‣ Both adrenaline and noradrenaline are produced from the
amino acid tyrosine, through multiple reactions
‣ The synthesized adrenaline is stored in vesicles before
being released into the blood stream
76. ADRENAL MEDULLA
FUNCTION
‣ Adrenaline is mainly associated with the “fight or flight response“,
and noradrenaline also plays a role in the activation of the
sympathetic nervous system as a neurotransmitter in post-ganglionic
synapses
‣ It exhibits its actions through α and β adrenoreceptors (G protein
coupled receptors), both in the central nervous system and in the
periphery
‣ The “fight or flight response” is a key survival mechanism, and causes
a number of physiological changes, such as increased cardiac
output and increased glycogenolysis in liver and muscle tissue
80. ADRENAL MEDULLA
REVIEW QUESTIONS
‣ What are the main secretory cells of the adrenal medulla?
‣ Chief cells
‣ Juxtaglomerular cells
‣ Chromaffin cells
‣ Kupffer cells
81. ADRENAL MEDULLA
REVIEW QUESTIONS
‣ What are the main secretory cells of the adrenal medulla?
‣ Chief cells
‣ Juxtaglomerular cells
‣ Chromaffin cells
‣ Kupffer cells
83. ADRENAL MEDULLA
REVIEW QUESTIONS
‣ What is the general mechanism for release of adrenaline from the
adrenal medulla?
‣ Stimulation of Chromaffin cells by a protein-based stimulating
hormone
‣ Stimulation of Chromaffin DNA transcription by steroid-based
stimulating hormone
‣ Stimulation of Chromaffin cells by sympathetic nervous system
directly
‣ Mechanism unknown
84. ADRENAL MEDULLA
REVIEW QUESTIONS
‣ What is the general mechanism for release of adrenaline from the
adrenal medulla?
‣ Stimulation of Chromaffin cells by a protein-based stimulating
hormone
‣ Stimulation of Chromaffin DNA transcription by steroid-based
stimulating hormone
‣ Stimulation of Chromaffin cells by sympathetic nervous
system directly
‣ Mechanism unknown
85. ADRENAL MEDULLA
REVIEW QUESTIONS
‣ Chromaffin cells are effectively the sympathetic ganglion -
they are innervated directly by the pre-ganglionic nerve
fibres (T5-T11)
86. ADRENAL MEDULLA
REVIEW QUESTIONS
‣ Which of the following is NOT synthesized in the adrenal
medulla?
‣ Noradrenaline
‣ Dopamine
‣ Adrenaline
‣ Phenylalanine
87. ADRENAL MEDULLA
REVIEW QUESTIONS
‣ Which of the following is NOT synthesized in the adrenal
medulla?
‣ Noradrenaline
‣ Dopamine
‣ Adrenaline
‣ Phenylalanine
88. ADRENAL MEDULLA
REVIEW QUESTIONS
‣ Phenylalanine is an essential amino acid that is gained
from the diet, rather than synthesised in humans. It is a
precursor for tyrosine, which is used to synthesise
dopamine, noradrenaline and adrenaline.
89. ADRENAL MEDULLA
REVIEW QUESTIONS
‣ Which of the following is a symptom of
phaechromocytoma?
‣ Hypotension
‣ Hypertension
‣ Hypoglycaemia
‣ Exophthalmos
90. ADRENAL MEDULLA
REVIEW QUESTIONS
‣ Which of the following is a symptom of
phaechromocytoma?
‣ Hypotension
‣ Hypertension
‣ Hypoglycaemia
‣ Exophthalmos
91. ADRENAL MEDULLA
REVIEW QUESTIONS
‣ The increased adrenaline synthesis and secretion give an
exaggerated sympathetic response. This causes a rise in
blood pressure.
92. References
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‣ https://teachmephysiology.com/endocrine-system/adrenal-glands/zona-
glomerulosa/
‣ https://teachmephysiology.com/endocrine-system/adrenal-glands/zona-fasciculata/
‣ https://teachmephysiology.com/endocrine-system/adrenal-glands/zona-reticularis/
‣ https://teachmephysiology.com/endocrine-system/adrenal-glands/adrenal-
medulla/
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