1. Lecture 1 Dr. Zahoor Ali Shaikh 1

2.  There are two Adrenal glands, one above each kidney.  Adrenal gland has outer cortex and inner medulla. - Outer cortex secrete – steroid hormones - Inner medulla secrete – catecholamine (Epinephrine, Nor epinephrine) 2

3.  Adrenal cortex and adrenal medulla secrete hormones which belong to different chemical categories, whose function mechanism of action and regulation are totally different. Therefore there are TWO endocrine organs in Adrenal gland.  We will discuss adrenal cortex and then adrenal medulla. 3

4.  Adrenal cortex secretes - Mineralocorticoids, Glucocorticoids, Sex hormones  Adrenal cortex has three layers 1. Zona glomerulousa [outer layer] – mineralocorticoid - aldosterone 2. Zona Fasciculata [middle layer] 3. Zona Reticularis [inner layer] 4 Glucocorticoids & Sex hormones

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6.  Adrenal cortex produces number of adrenocortical hormones, all of which are steroids derived from cholesterol.  Cholesterol is converted to pregnenolone and then by enzymatic action on pregnenolone, steroid hormones are produced. 6

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8.  Adrenal steroid hormones can be divided into three categories: 1. Mineralocorticoids – Aldosterone, it affects mineral that is electrolyte balance [Na +, K + balance]. 2. Glucocorticoids – Cortisol, plays major role in glucose metabolism but also in protein, lipid metabolism and in stress situation. 3. Sex hormones - Testosterone [male sex hormone] - Estrogen [female sex hormone] 8

9.  Adrenal Steroid hormones [Aldosterone, Glucocorticoids, sex hormones] are all lipophilic, therefore, immediately diffuse through plasma membrane of the cell into the blood.  In the blood, - Corticosteroids are carried by Alpha globulin [transcortin]. - Aldosterone and Dehydroepiandrosterone [DHEA] are carried by albumin. 9

10. Aldosterone Action & Function  Aldosterone acts on the distal convoluted tubule and collecting tubule of the kidney and causes Na + absorption and K + excretion.  Na + retention causes osmotic retention of water and expands ECF [Extra cellular fluid], which is important in long term regulation of blood pressure. 10

11.  Mineralocorticoids are essential for life. WHY ?  Because when Mineralocorticoids are NOT there, there will be decrease plasma volume due to decreased Na + and H 2 O. It will lead to decreased Blood Pressure and circulatory failure. 11

12.  Control of Aldosterone secretion is through 1. Renin-Angiotensin-Aldosterone system [RAAS] which is regulated by decrease in Na + and decrease in blood pressure. 2. Direct Stimulation of Adrenal cortex by rise in plasma K + concentration 12

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14.  ACTH from anterior pituitary gland promotes the secretion of Cortisol, but not Aldosterone, therefore regulation of Aldosterone is largely independent of anterior pituitary control. 14

15. GLUCOCORTICOID  We will see 1. Metabolic Effects 2. Role in Adaptation of Stress 1. Metabolic Effects Cortisol plays important role in carbohydrate, protein and fat metabolism. 15

16.  Main function of Glucocorticoids is to increase blood glucose level. HOW ?  By Gluconeogenesis – conversion of non- carbohydrate sources e.g. amino acids into carbohydrate within the liver.  Gluconeogenesis helps to maintain hepatic glycogen stores. Between meals or during fasting glycogen releases glucose in the blood to maintain glucose level. 16

17.  Glucocorticoids inhibit glucose uptake by the tissues but not the brain, as brain uses only glucose as its metabolic fuel.  Glucocorticoids stimulate protein breakdown in many tissues especially muscle.  Glucocorticoids facilitate lipolysis [breakdown of lipid], therefore release fatty acid. 17

18.  Cortisol permits catecholamine to induce vasoconstriction.  Lack of Cortisol may cause circulatory shock. NOTE If any patient is on Cortisol and undergoes surgery, the dose of Cortisol should be increased. 18

19. How Cortisol helps to adapt to stress ?  Precise role is not known, but possible explanation might be In case of stress e.g. surgery, accident, etc. - Increased glucose level by Cortisol will help brain to work [As patient is not eating]. - Increased amino acid by Cortisol will help in tissue repair. - Increased fatty acids available are used by tissue as alternate fuel. 19

20. 1. Anti inflammatory Cortisol blocks the production of inflammatory chemical mediators e.g. leukotrines, prostaglandin. - Cortisol suppresses migration of nuetrophil to the injured side. 2. Immunosuppressive Cortisol inhibits immune response by interfering with antibody production by lymphocytes. 20

21.  We use corticosteroids when inflammatory response itself has become destructive e.g. rheumatoid arthritis.  In preventing organ transplant rejection. 21

22.  As immune response of the body are suppressed, person has more chances to get infection. OTHER SIDE EFFECTS - Gastric ulcer - High Blood pressure - High Blood sugar - Bone Osteoporosis - Menstrual irregularities 22

23.  Cortisol secretion is regulated by ACTH, through negative feedback loop involving Hypothalamus – pituitary – adrenal cortex axis.  ACTH acts on Zona Fasciculate and Zona Rectilularis. 23

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25.  Diurnal or Circadian Rhythm Effect Cortisol level is high in the morning [awake] and low at the night [during sleep]. - Circadian Rhythm is regulated by biological clock [suprachismatic nuclei] of Hypothalamus and is related to sleep – wake cycle. - Peak and low level are reversed in person who works at night and sleeps during the day. 25

26.  In both sexes [male and female] adrenal cortex produces both androgens [male sex hormone] and estrogens [female sex hormone].  Under normal conditions, adrenal androgens and estrogens are not so abundant to induce masculinizing or feminizing effects. 26

27.  In female, adrenal androgen is responsible for androgen dependent processes  e.g. pubertal growth spurt,  Growth of axillary and pubic hair.  Development and maintenance of sex drive 27

28.  It is ACTH that controls adrenal androgen secretion [not the pituitary gnadotropic hormone].  In female, at the time of puberty, adrenal androgen secretion increases which initiates the development of androgen dependent processes. 28

29.  Adrenal Gland – Layers  Secretion of Steroids Hormones by each layer  Aldosterone – Action & Function  Control of Aldosterone Secretion  Glucocorticoids – metabolic effects, role in stress  Glucocorticoids other effects Anti-inflammatory and Immunosuppressive  Side Effects of Corticoids  Regulation of Cortisol Secretion, Diurnal Rhythm  Secretion of Sex hormones by adrenal cortex and their control 29

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