DR.MOUAADH ABDELKARIM ASSISTANT PROFESSOR OF PHYSIOLOGY COLLEGE OF MEDICINE KING SAUD UNIVERSITY Endocrinology Adrenal Gland College of Dentistry

Adrenal Glands Adrenal glands are paired, pyramid- shaped organs at the top of the kidneys Structurally and functionally, they are two glands in one:  Adrenal medulla (20%)  Adrenal cortex (80%) Cortex Medulla

lactotrophs Thyrotrophs Somatotrophs Corticotrophs Gonadotrophs Adrenal Cortex & ACTH Hormone Corticotropin releasing hormone adrenocorticotropic hormone

Adrenal Cortex Synthesizes and secretes steroid hormones called corticosteroids (Adrenocorticoids). Different Corticosteroids are produced in each of the three layers:  Zona glomerulosa – Mineralocorticoids (Aldosterone)  Zona fasciculata – Glucocorticoids (Cortisol)  Zona reticularis – Androgens

Adrenal Cortex

Steroid Hormones: Structure

Steroid Hormones Synthesis Steroids are derivatives of cholesterol Steroid hormones are synthesized and secreted on demand (not stored) The first step in the synthesis of all steroid hormones is conversion of cholesterol to different types of steroids by the enzyme cholesterol desmolase Newly synthesized steroid hormones are rapidly secreted from the cell Following secretion, all steroids bind to some extent to plasma proteins: CBG and albumin

Mineralocorticoids Regulate the electrolyte concentrations of extracellular fluids (ECF) Aldosterone – is the most important mineralocorticoid hormone  Maintains Na + balance by reducing excretion of Na + from the body  Stimulates reabsorption of Na + by the distal tubule and collecting duct in kidneys  Stimulates the active secretion of potassium from the tubular cell into the urine.  It also stimulates sodium & potassium transport in sweat glands, salivary glands, & intestinal epithelial cells.

Regulation of Aldosterone secretion Aldosterone secretion is stimulated by:  Decreasing blood volume or pressure (renin-angeotensin system) is the major stimulant  Rising blood levels of K +  Low blood Na +  ACTH

Glucocorticoids (Cortisol) Help the body resist stress by:  Glucocorticoids are essential for life, without them the person will die  Without Glucocorticoids, the body cannot cope with even mild stressors Cortisol promotes:  Gluconeogenesis (formation of glucose from noncarbohydrates).  Rises in blood glucose, fatty acids, and amino acids.  Mobilization of amino acids from proteins  Lipolysis

Glucocorticoids (Cortisol) o Maintain normal renal function o Blood pressure regulation & cardiovascular function: Sensitizes arterioles to catecholamines (Permissive effect) o Suppression of immune response and anti-inflammatory effects o Inhibit bone formation o Decrease REM sleep Effects on CNS: Negative feedback control on release of ACTH and modulates perception & emotion Target tissues: most body tissues

Functions of cortisol in stress and inflammation Any type of stress whether physical or neurogenic stimulates ACTH secretion and hence stimulate the adrenals to secrete cortisol. Mechanism of action in the stress:- Glucocorticoids cause rapid mobilization of amino acids and fats from their stores, making them available for energy and for synthesis of other compounds needed by different tissues of the body during stress. Anti-inflammatory effects of Cortisol During tissue damage by trauma or infection, tissues became inflamed due to the release of the intracellular lysosomal enzymes stored in the lysosomes. Cortisol stabilization of the intracellular lysozomal membranes (protect from rupture) release of proteolytic enzymes inflammation. Exogenous glucocorticoids are used in the treatment of asthma and rheumatoid arthritis

CRH from hypothalamus is the major regulator of ACTH secretion ACTH from anterior pituitary stimulates cortisol synthesis and secretion CRH (and ACTH) are secreted in pulses Glucocorticoids (cont.)

Regulation of Cortisol secretion  The secretion of cortisol by zona fasciculata is regulated exclusively by the hypothalamic- pituitary axis

Circadian rhythm of cortisol secretion  The greatest cortisol secretory activity occurs in the early morning hours and diminish late in the afternoon.

Adrenal Androgens -The most important of which is dehydroepiandrosterone (DHEA). - Are continually secreted by the adrenal cortex, especially during fetal life. - Have only weak effects in humans. - Participate in the early development of the male sex organs in childhood. - Growth of the pubic and axillary hair in the females. - In extra-adrenal tissues, some of the adrenal androgens are converted to testosterone which probably accounts for much of their androgenic activity.

Disorders of Adrenal Cortex

Cushing’s Syndrome Cushing’s syndrome results from continued high levels of glucocorticoids. Causes:  pituitary adenoma 75-90%  adrenal adenoma, carcinoma  over-secretion of ACTH  high pharmacological doses of exogenous glucocorticoids Characterized by changes in carbohydrates and protein metabolism, hyperglycemia, hypertension, and muscle weakness.

Cushing’s Syndrome Signs:  Fat is deposited in the body trunk (central obesity)  Buffalo hump  Moon face (subcutaneus fat in cheeks and submandibular)  Purple (red) striae  Blood-glucose levels rises chronically, causing adrenal diabetes

primary aldosteronism In primary aldosteronism, your adrenal glands produce too much aldosterone, causing you to lose potassium and retain sodium. The excess sodium in turn holds onto water, increasing your blood volume and blood pressure. Primary hyperaldosteronism has many causes, including adrenal hyperplasia and adrenal carcinoma. Conn's syndromehyperaldosteronismhyperplasia carcinomaConn's syndrome

Hypofunction of the Adrenals (Addison’s Disease/Hypoadrenalism) Causes of adrenal hypofunction include: autoimmune disorders tumors infection abrupt withdrawal of long-term steroids surgery chronic or extreme acute stress that depletes or exhausts the bodies steroid stores Decreased ECF volume.

Adrenal Medulla

Produces epinephrine (80%) Produces norepinephrine (20%)  They are released from chromaffin cells Secretion of these hormones causes:  Blood to be diverted to the brain, heart, and skeletal muscle Catecholamines

Effects of Catecholamines 1- Glycogenolysis in liver and skeletal muscle (can lead to hyperglycemia) which increases blood glucose level 2- Increase heart rate and blood pressure 3- Cause vasoconstriction of blood vessels 4- Mobilization of free fatty acids 5- Increase metabolic rate 6- Increase O 2 consumption

Stress and the Adrenal Gland