This document discusses corticosteroids and the endocrine, reproductive, and urinary systems. It covers the learning objectives, which include defining the endocrine system and hormones like corticosteroids, glucocorticoids, and mineralocorticoids. It describes hormone production in the suprarenal (adrenal) gland and corticosteroid biosynthesis. The roles and mechanisms of action of corticosteroids are explained. The effects of glucocorticoids and mineralocorticoids on metabolism, protein regulation, and sodium/potassium balance are summarized. Disorders of the adrenal glands like Cushing's syndrome and Addison's disease are also mentioned.

1. NSB 212: Endocrine, Reproductive
and Urinary System
TOPIC : Corticosteroids
• GLUCOCORTICOIDS
• MINERALOCORTICOIDS
Dr. G.K. Maiyoh
GKM/NSB212/ENDOCRINE,REPR
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2. Learning objectives
• Define the endocrine sys, hormones,
corticosteriods, glucocoticoids and
mineralocorticoids
• Suprarenal gland and hormone production
• Corticosteroid biosynthesis
• Roles of Corticosteroids and mechanism of
action
• Renal Biochemistry
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3. Endocrine system (ES)
The ES together with the nervous system,
acts as the body´s communication
network
- It is composed of various endocrine
glands and endocrine cells
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4. Endocrine system
- The glands are capable
of synthesizing and
releasing special
chemical messengers -
hormones
• Unlike the nervous
system, the endocrine
system is anatomically
discontinuous.
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5. Hormones
• Are substances which are secreted by
specialised cells in very low
concentrations and they are able to
influence
EITHER;
secreting cell itself (autocrine
influence), adjacent cells (paracrine
influence) or remote cells (hormonal
influence)
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6. Corticosteroids
• Hormones that are produced from the Adrenal
cortex
• They are synthesized from enzymatic
modification of cholesterol
• Two categories;
– Glucocoticoids
– Mineralocorticoids
– Similar structurally but dramatically different
functionally
Cholesterol
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8. Suprarenal Glands
• Also called Adrenal glands
• 4grams each
• Divided into two parts;
each with separate functions
– Suprarenal Cortex
– Suprarenal Medulla
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9. The Adrenal Cortex
Figure 25.9a
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10. Glucocorticoids - defined
• Are so referred because they were seen to
increase the levels of plasma glucose
• Made in the fasciculata and reticularis layer
near cortical medullary junction
• Cortisol is the major glucocorticoid
• Cortisol deficiency can therefore result in
hypoglycemia (below normal levels of
blood glucose)
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11. Glucocorticoids
Cortisol
(Hydrocortiso
ne)
Corticosterone
Cortisone

12. • Glucocorticoids
• Glucocorticoids (naturally
occurring; cortisol --
hydrocortisone)

13. • · Pharmacokinetics:
• Synthesis:
• § major glucocorticoid: cortisol
• § precursor: cholesterol

14. Cholesterol
Pregnenolone
Progesterone
Corticosterone
11-Deoxy-
corticosterone
18-Hydroxy-
corticosterone
ALDOSTERONE
17-α- Hydroxy
pregnenolone
11- Deoxy- cortisol
17- Hydroxy
progesterone
21,β hydroxylase
CORTISOL
11,β hydroxylase
Dehydro-epi
androsterone
Andro-
stenedione
Oestrone
Oestriol
TESTOSTERONE OESTRADIOL
ACTH
BIOSYNTHESIS
17 α-Hydroxylase
17 α-Hydroxylase
DE
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15. Enzymes for Aldosterone synthesis
DE Deh.
Cholesterol Pregnenolone Progesterone
(21)
Aldosterone (18) corticosterone (11) Deoxy-
corticosterone
DE= debranching enzyme; side chain cleavage enzyme;
desmolase
Deh.= 3β-hydroxysteroid dehydrogenase enzyme
21 = 21α hydroxylase
11 = 11 β-hydroxylase
18 = Aldosterone synthase
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16. physiology

17. Figure 21.15
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18. physiology
• The hypothalamus releases a hormone
called corticotropin-releasing-hormone
(CRH).
• The CRH then travels directly to the
pituitary gland where they cause the
release of adrenocorticotropic hormone
(ACTH).

19. physiology
• ACTH is released into the bloodstream.
• Once in the blood, ACTH travels to the
adrenal cortex where it effects the release
of corticosteroids.

20. physiology
• However, as well as these excitatory
processes, there are also inhibitory influences
within the Hypothalamopituitary adrenal
(HPA).
• These inhibitory influences act on CRH
neurons and also in the pituitary.
• The result of such inhibitions is to reduce the
release of ACTH.

21. GKM/NSB212/ENDOCRINE,REPR
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22. Mechanism of Action:
• Glucocorticoid action through
glucocorticoid receptors

23. 75% of cortisol bound to plasma proteins
cortisol half-life: about 60-90 minutes

25. Cortisol metabolism:
--20% converted to cortisone (by renal/other tissues
with mineralocorticoid receptors)
• --- Catalyzed by 11-hydroxysteroid dehydrogenase
 ---Cortisol and cortisone inactivated in the liver by
conversion (3-hydroxysteroid dehydrogenase
catalyzed)

26. Some metabolites ultimately excreted in
the urine as 11-oxy, 17-ketosteroids
---Some metabolites undergo hepatic
conjugation to form glucuronic acid or
sulfate derivatives

27. Physiological effects of
glucocorticoids
 Major metabolic effects: due to direct
cellular action
• ---Some effects:secondary to homeostatic
insulin and glucagon responses
 Physiological responses modulated by
glucocorticoids ("permissive" effects)
• --- catecholamine vascular/bronchial smooth
muscle response:

28. Metabolic Effects
 Glucocorticoids: stimulate and are required
for:
---gluconeogenesis (fasted state, diabetes);
---increasing hepatic and renal amino acid
uptake
--- increase gluconeogenic enzyme activity
 Hepatic effects:
--- Simulation of glycogen synthase
- ---Increase glucose production from protein
- --- stimulating insulin release

29. Metabolic Effects
 Adipocytes:
—inhibit glucose uptake promoting increased lipolysis
— counteracted by enhanced insulin secretion which
stimulates lipogenesis
 Glucocorticoid effects are most prominent in the fasting
state, through:
—stimulation:gluconeogenesis
— stimulation: amino acid release from muscle
(catabolism)
—inhibition: peripheral glucose uptake
— stimulation: lipolysis

30.  promotion of catabolism:
—lymphoid tissue
— connective tissue
— muscle
— fat
— skin
 High (supraphysiologic) glucocorticoid levels cause:
— decreased muscle mass, weakness
 Reduced growth in children (not prevented by growth
hormone)
Catabolic Effects

31.  Catabolic effects on bone
• ---osteoporosis in Cushing's syndrome
• ----major limitation in long-term use
• Osteoporosis:
A disease in which the bones become extremely
porous, are subject to fracture, and heal
slowly

32. Glucocorticoids,
Catecholamines, etc..
Muscle:
Net loss of amino
Acids (glucose)
Liver:
Deamination of
amino acids,
gluconeogenesis
(glucose)
Fat Cells:
Free fatty
acid
mobilization
Heart rate:
Increased
Immune
system:
altered
Adrenals
Kidney
Posterior
Pituitary Gland
Hypothalamus
Anterior
Pituitary Gland
ACTH
Stress
Circadian
rhythm
CRH
(-)
Glucocorticoids,
Catecholamines, etc..
Hypothalamopituitary adrenal (HPA) axis: Negative
Feedback
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33. Mineralocorticoids
• Synthesized in the glomerulosa
• Aldosterone is the major mineralocorticoid
hormone
• Considered mineralocorticoid because it
promotes salt and water retention in the
kidneys
• Steriod hormones: Glucocorticoids,
mineralocorticoids and sex steroids
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35. Functions of mineralocorticoids
• Aldosterone exerts the 90% of the
mineralocorticoid activity. Cortisol also have
mineralocorticoid activity, but only 1/400th
that
of aldosterone
• Aldosterone increases renal tubular (principal
cells) reabsorption of sodium & secretion of
potassium
• Excess aldosterone ↑ ECF volume & arterial
pressure, but has only a small effect on plasma
sodium concentration
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36. GKM/NSB212/ENDOCRINE,REPR
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Body Fluid Compartments
• In lean adults, body fluids constitute 55% of
female and 60% of male total body mass
– Intracellular fluid (ICF) inside cells
• About 2/3 of body fluid
– Extracellular fluid (ECF) outside cells
• Interstitial fluid between cell is 80% of ECF
• Plasma in blood is 20% of ECF
– Also includes lymph, cerebrospinal fluid, synovial fluid,
aqueous humor, vitreous body, endolymph, perilymph, pleural,
pericardial, and peritoneal fluids

37. GKM/NSB212/ENDOCRINE,REPR
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Body Fluid Compartments

38. • Excess aldosterone causes hypokalemia &
muscle weakness, & too little aldosterone
causes hyperkalemia & cardiac toxicity
• Excess aldosterone increases tubular
(intercalated cells) hydrogen ion secretion,
with resultant mild alkalosis
• Aldosterone stimulates sodium & potassium
transport in sweat glands, salivary glands, &
intestinal epithelial cells
Functions of mineralocorticoids
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39. Effect of cortisol on protein metabolism
• Reduction of protein storage in all cells except
those of liver – ↑ protein catabolism & ↓ protein
synthesis
• Cortisol increases liver & plasma proteins
• Mobilizes aminoacids from non hepatic cells, thus
increase blood amino acid level.
• ↑ amino acid transport to liver cells & ↓ transport
of amino acids into other cells
Functions of glucocorticoids
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40. Mechanisms of action
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41. Corticosteroids are Gene-Active
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42. Effects of Stress and The Adrenal Glands
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43. REGULATION OF CORTISOL SECRETION
INCREASED
BLOOD GLUCOSE
BLOOD AA
BLOOD FATTY ACIDS
HYPOTHALAMUS
CRH
ANTERIOR PITUITARY
ACTH
ADRENAL CORTEX
TARGET ORGANS
CORTISOL
STRESS
DIURNAL
RHYTHM
+ +-
-
Negative
Feed-back
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44. Renal Biochemistry (Mineralocorticoids role)
Renin-angiotensin-aldosterone axis
Angiotensinogen
Renin
Angiotensin I
ACE
Angiotensin II
Aldosterone
ACE = Angiotensin converting enzyme

45. Renin-angiotensin-aldosterone axis
• Principal factor
controlling Ang II
levels is renin
release.
• Decreased
circulating volume
stimulates renin
release via:
– Decreased BP
(sensed by JGA).
– Decreased [NaCl] at
macula densa
(“NaCl sensor”)
– Decreased renal
perfusion pressure
(“renal”
baroreceptor) GKM/NSB212/ENDOCRINE,REPR
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46. GKM/NSB212/ENDOCRINE,REPR
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47. Figure 6.12b
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48. • Atrial natriuretic peptide
• Decreased blood pressure
stimulates renin secretion
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49. Renin
Aldosterone
Adrenal
cortex
Corticosterone
Angiotensinogen
(Lungs)
↓ renal blood flow &/or ↓ Na+
++ Juxtaglomerular apparatus of kidneys
(considered volume receptors)
Angiotensin I
Converting
enzymes
Angiotensin II
(powerful vasoconstrictor)
Angiotensin III
(powerful vasoconstrictor)
• Renin-Angiotensin System:
N.B. Aldosterone is the main regulator of Na+
retention.

50. Renin-Angiotension-Aldosterone System

51. Disorders of the Adrenal Gland
1. Hypoaldosteronism
results in excess loss of water/Na+
Addison’s disease – low aldosterone & cortisol
2. Hyperaldosteronism
3. Cushing’s syndrome
hypersecretion of cortisol,androgens,aldosterone
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52. Adrenal glands can malfunction
• Cushing syndrome – hypersecretion of
glucocorticoids by the adrenal cortex characterized by
weight gain in the trunk of the body but not arms and
legs1`
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53. GKM/NSB212/ENDOCRINE,REPR
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54. Cushing’s Disease
• Proximal muscle wasting &
weakness
• Osteoporosis
• Glucose intolerance
• HTN, hypokalemia
• Thromboembolism
• Depression, Psyc
• Infection
• Glaucoma
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55. Adrenal glands can malfunction
• Addison’s disease – hyposecretion of
glucocorticoids by the adrenal cortex characterized
by bronzing of the skin
15.4 Adrenal glands
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56. GKM/NSB212/ENDOCRINE,REPR
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