{"id":4422384,"date":"2025-01-11T15:58:17","date_gmt":"2025-01-11T21:58:17","guid":{"rendered":"https:\/\/myendoconsult.com\/learn\/topics\/physiology-of-the-adrenal-gland\/"},"modified":"2025-01-12T18:22:34","modified_gmt":"2025-01-13T00:22:34","slug":"physiology-of-the-adrenal-gland","status":"publish","type":"oen_topic","link":"https:\/\/myendoconsult.com\/learn\/topics\/physiology-of-the-adrenal-gland\/","title":{"rendered":"Physiology of the Adrenal Gland"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\">BIOSYNTHESIS AND METABOLISM OF ADRENAL CORTICAL HORMONES<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Overview of Adrenal Steroids<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Steroids of the Adrenal Cortex<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Glucocorticoids<\/strong> (cortisol)<\/li>\n\n\n\n<li><strong>Mineralocorticoids<\/strong> (aldosterone)<\/li>\n\n\n\n<li><strong>Adrenal Androgens<\/strong> (17-ketosteroids, e.g., DHEA, androstenedione)<\/li>\n\n\n\n<li><strong>Estrogens<\/strong><\/li>\n\n\n\n<li><strong>Progestogens<\/strong><\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Functional Regulation<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong><a href=\"https:\/\/myendoconsult.com\/learn\/zona-fasciculata-of-the-adrenal-gland\/\" data-wpil-monitor-id=\"156\">Zona Fasciculata<\/a> &amp; Zona Reticularis<\/strong>: Regulated by pituitary corticotropin (ACTH).<\/li>\n\n\n\n<li><strong><a href=\"https:\/\/myendoconsult.com\/learn\/the-zona-glomerulosa-of-the-adrenal-gland\/\" data-wpil-monitor-id=\"157\">Zona Glomerulosa<\/a><\/strong>: Aldosterone secretion regulated mainly by <strong>angiotensin II<\/strong> &amp; <strong>potassium<\/strong>, with minor ACTH influence.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">ACTH Regulation and Diurnal Rhythm<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Negative Feedback<\/strong>\n<ul class=\"wp-block-list\">\n<li>Decreased blood cortisol \u2192 increased CRH &amp; ACTH \u2192 raised cortisol levels \u2192 inhibitory feedback on CRH &amp; ACTH.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Diurnal (Circadian) Variation<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Maximal ACTH secretion<\/strong> (pulse frequency\/amplitude) between <strong>2\u20138 am<\/strong>.<\/li>\n\n\n\n<li>Gradual daytime decrease, lowest in late evening.<\/li>\n\n\n\n<li>Dependent on <strong>sleep\u2013wake<\/strong> and <strong>light\u2013dark<\/strong> cycles; resets over 10\u201314 days with major time zone changes.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Response to Stress<\/strong>\n<ul class=\"wp-block-list\">\n<li>Stress (fever, trauma, hypoglycemia, hypotension) overrides feedback, <a href=\"https:\/\/myendoconsult.com\/learn\/acth-stimulation-test\/\" data-wpil-monitor-id=\"158\">stimulating high ACTH<\/a> and increased cortisol (up to ~250 mg\/day).<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"3375\" height=\"3375\" src=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/Circadian-Rhythm.png\" alt=\"\" class=\"wp-image-4422822\" srcset=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/Circadian-Rhythm.png 3375w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/Circadian-Rhythm-300x300.png 300w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/Circadian-Rhythm-150x150.png 150w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/Circadian-Rhythm-768x768.png 768w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/Circadian-Rhythm-1536x1536.png 1536w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/Circadian-Rhythm-2048x2048.png 2048w\" sizes=\"auto, (max-width: 3375px) 100vw, 3375px\" \/><figcaption class=\"wp-element-caption\">Normal Circadian Rhythm<\/figcaption><\/figure>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">Synthesis Pathway of Cortical Steroids<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Cholesterol Sources and Modifications<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cholesterol<\/strong> derived from acetate, stored in <a href=\"https:\/\/myendoconsult.com\/learn\/the-formation-and-structure-of-the-adrenal-cortex\/\" data-wpil-monitor-id=\"159\">adrenal cortex<\/a>.<\/li>\n\n\n\n<li><strong>Cyclopentanoperhydrophenanthrene nucleus<\/strong> (3 cyclohexane rings + 1 cyclopentane ring).<\/li>\n\n\n\n<li>Enzymes introduce hydroxyls or remove hydrogen (oxidation).<\/li>\n\n\n\n<li><strong>Glucocorticoids<\/strong>: Have \u03b1-ketol group &amp; 11-hydroxyl group.<\/li>\n\n\n\n<li><strong>First Step<\/strong>: Cleavage of cholesterol into <strong>pregnenolone<\/strong> (C21 precursor of all steroid hormones) + isocaproaldehyde.\n<ul class=\"wp-block-list\">\n<li>Occurs in adrenal cortex, testicular Leydig cells, ovarian theca cells, trophoblasts, some brain cells.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Steroid Class by Carbon Number<\/strong>\n<ul class=\"wp-block-list\">\n<li>C21: Glucocorticoids, progestogens<\/li>\n\n\n\n<li>C19: Androgens<\/li>\n\n\n\n<li>C18: Estrogens<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"3000\" height=\"2100\" src=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/adrenal-steroidogenesis.png\" alt=\"\" class=\"wp-image-4422811\" srcset=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/adrenal-steroidogenesis.png 3000w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/adrenal-steroidogenesis-300x210.png 300w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/adrenal-steroidogenesis-768x538.png 768w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/adrenal-steroidogenesis-1536x1075.png 1536w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/adrenal-steroidogenesis-2048x1434.png 2048w\" sizes=\"auto, (max-width: 3000px) 100vw, 3000px\" \/><figcaption class=\"wp-element-caption\">Adrenal Steroidogenesis<\/figcaption><\/figure>\n\n\n\n<h3 class=\"wp-block-heading\">Key Enzymes and Locations<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Steroidogenic Acute Regulatory Protein (StAR)<\/strong>\n<ul class=\"wp-block-list\">\n<li>Transports cholesterol from outer to inner mitochondrial membrane.<\/li>\n\n\n\n<li>Induced by \u2191cAMP after <strong>ACTH<\/strong> receptor activation.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>P450scc (Side-Chain Cleavage)<\/strong>\n<ul class=\"wp-block-list\">\n<li>Located in mitochondria, converts cholesterol \u2192 pregnenolone.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Electron Shuttles<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Adrenodoxin\/Adrenodoxin Reductase<\/strong> for mitochondrial P450 enzymes (P450scc, 11\u03b2-hydroxylase, aldosterone synthase).<\/li>\n\n\n\n<li><strong>P450 oxidoreductase (P450 OR)<\/strong> for endoplasmic reticulum enzymes (17\u03b1-hydroxylase, 21-hydroxylase).<\/li>\n\n\n\n<li><strong>Cytochrome b5<\/strong> facilitates 17,20-lyase activity of P450c17.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Hydroxysteroid Dehydrogenases<\/strong>\n<ul class=\"wp-block-list\">\n<li>E.g., 3\u03b2-HSD, convert pregnenolone \u2192 progesterone, DHEA \u2192 androstenedione, etc.<\/li>\n\n\n\n<li>Reactions are often reversible (unlike P450 hydroxylations).<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<h3 class=\"wp-block-heading\">Pathway Details in Adrenal Cortex<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Zona Glomerulosa<\/strong>\n<ul class=\"wp-block-list\">\n<li>Lacks 17\u03b1-hydroxylase (P450c17).<\/li>\n\n\n\n<li>Produces <strong>aldosterone<\/strong> via <strong>aldosterone synthase (CYP11B2)<\/strong>.<\/li>\n\n\n\n<li>Key steps:\n<ul class=\"wp-block-list\">\n<li>21-hydroxylation of progesterone \u2192 <strong>deoxycorticosterone<\/strong> (DOC), then 11\u03b2-hydroxylation \u2192 <strong>corticosterone<\/strong>, then 18-hydroxylation \u2192 <strong>aldosterone<\/strong>.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Zona Fasciculata<\/strong>\n<ul class=\"wp-block-list\">\n<li>Has <strong>17\u03b1-hydroxylase<\/strong> \u2192 forms <strong>17-hydroxyprogesterone<\/strong> \u2192 21-hydroxylase \u2192 <strong>11-deoxycortisol<\/strong> \u2192 11\u03b2-hydroxylase \u2192 <strong>cortisol<\/strong>.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Zona Reticularis<\/strong>\n<ul class=\"wp-block-list\">\n<li>High <strong>17,20-lyase<\/strong> activity (P450c17 with cytochrome b5).<\/li>\n\n\n\n<li>Produces <strong>DHEA<\/strong> (dehydroepiandrosterone) + androstenedione.<\/li>\n\n\n\n<li>DHEA can be sulfated (DHEA-S) by SULT2A1 or converted to androstenedione by 3\u03b2-HSD.<\/li>\n\n\n\n<li>Minor testosterone production by 17\u03b2-HSD3.<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<h3 class=\"wp-block-heading\">Normal Secretion Rates<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Cortisol<\/strong>: 10\u201320 mg\/day<\/li>\n\n\n\n<li><strong>Aldosterone<\/strong>: 0.1\u20130.15 mg\/day<\/li>\n\n\n\n<li><strong>DHEA<\/strong>: ~4 mg\/day, <strong>DHEA-S<\/strong>: 10 mg\/day, <strong>Androstenedione<\/strong>: 1.5 mg\/day, <strong>Testosterone<\/strong>: 0.05 mg\/day.<\/li>\n\n\n\n<li>Adrenal androgens have lower potency vs. gonadal testosterone.<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">Metabolism of Cortisol and Aldosterone<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Cortisol Binding and Interconversion<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>90% Bound<\/strong> in plasma (CBG &gt; albumin).\n<ul class=\"wp-block-list\">\n<li>CBG\u2191 with oral estrogen, pregnancy, active hepatitis.<\/li>\n\n\n\n<li>CBG\u2193 with cirrhosis, nephrotic syndrome, multiple myeloma, hyperthyroidism.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Half-Life<\/strong>: ~60\u2013120 minutes.<\/li>\n\n\n\n<li><strong>11\u03b2-Hydroxysteroid Dehydrogenase (11\u03b2-HSD)<\/strong> Isozymes\n<ul class=\"wp-block-list\">\n<li><strong>Type 1<\/strong> (11\u03b2-HSD1): Liver, converts <strong><a href=\"https:\/\/myendoconsult.com\/learn\/cortisol-cortisone-shunt\/\" data-wpil-monitor-id=\"153\">cortisone \u2192 cortisol<\/a><\/strong> (activating).<\/li>\n\n\n\n<li><strong>Type 2<\/strong> (11\u03b2-HSD2): Kidney, inactivates <strong>cortisol \u2192 cortisone<\/strong> to protect mineralocorticoid receptor (MR).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Apparent Mineralocorticoid Excess (AME)<\/strong>\n<ul class=\"wp-block-list\">\n<li>Deficient or inhibited 11\u03b2-HSD2 \u2192 cortisol excess at MR \u2192 hypertension, hypokalemia, low renin, low aldosterone.<\/li>\n\n\n\n<li>May be hereditary or due to inhibition by glycyrrhizic acid (licorice).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Further Metabolism<\/strong>\n<ul class=\"wp-block-list\">\n<li>Cortisol\/cortisone \u2192 reduced to <strong>tetrahydrometabolites<\/strong> (tetrahydrocortisol, tetrahydrocortisone), conjugated with glucuronic acid \u2192 excreted in urine.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Aldosterone Metabolism<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Liver: Aldosterone \u2192 <strong>tetrahydroaldosterone<\/strong> \u2192 excreted as <strong>3-glucuronide<\/strong> conjugates (20\u201330 \u03bcg\/day in urine).<\/li>\n\n\n\n<li>Small fraction appears in free form (1\u20135 \u03bcg\/day).<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">BIOLOGIC ACTIONS OF CORTISOL<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Carbohydrate, Protein, and Lipid Metabolism<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Hyperglycemic Effects<\/strong>\n<ul class=\"wp-block-list\">\n<li>\u2191Glycogen deposition (liver).<\/li>\n\n\n\n<li>\u2191Gluconeogenesis enzymes (glucose-6-phosphatase, phosphoenolpyruvate carboxykinase).<\/li>\n\n\n\n<li>\u2191Lipolysis (adipose) \u2192 \u2191free fatty acids.<\/li>\n\n\n\n<li>Facilitates <a href=\"https:\/\/myendoconsult.com\/learn\/homa-ir-calculator\/\" data-wpil-monitor-id=\"154\">insulin resistance<\/a> (synergistic with glucagon, catecholamines).<\/li>\n\n\n\n<li><strong>Excess<\/strong> \u2192 Diabetogenic, central adiposity.<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<h3 class=\"wp-block-heading\">Skin, Muscle, and Connective Tissues<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Catabolic<\/strong> in excess: diverts AAs from muscle \u2192 liver.<\/li>\n\n\n\n<li>Muscle wasting, proximal muscle weakness.<\/li>\n\n\n\n<li>Decreased collagen synthesis, inhibited epidermal cell division \u2192 thin skin, poor wound healing.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Bone and Calcium Metabolism<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Osteopenia\/Osteoporosis<\/strong> from \u2193osteoblast function, \u2191bone resorption.<\/li>\n\n\n\n<li>Risk of <strong>osteonecrosis<\/strong> (avascular necrosis), especially femoral head.<\/li>\n\n\n\n<li>\u2193Intestinal Ca\u00b2\u207a absorption, \u2191Renal Ca\u00b2\u207a <a href=\"https:\/\/myendoconsult.com\/learn\/fractional-excretion-of-calcium-calculator\/\" data-wpil-monitor-id=\"155\">excretion \u2192 negative calcium<\/a> balance.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Blood Pressure Control<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>\u2191GFR, \u2191Proximal tubular Na\u207a reabsorption, \u2191free water clearance.<\/li>\n\n\n\n<li><strong>Mineralocorticoid Receptor Overload<\/strong> if 11\u03b2-HSD2 is overwhelmed, leading to salt retention, hypokalemia.<\/li>\n\n\n\n<li>Enhances vascular reactivity to catecholamines, angiotensin II.<\/li>\n\n\n\n<li>Increases angiotensinogen synthesis.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Anti-Inflammatory and Immunosuppressive Actions<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>\u2193Blood lymphocytes (redistribution to lymph nodes, spleen).<\/li>\n\n\n\n<li>\u2193Immunoglobulin synthesis, \u2193Cytokine production, \u2191Lymphocyte apoptosis.<\/li>\n\n\n\n<li>\u2191Neutrophils, \u2193Eosinophils.<\/li>\n\n\n\n<li>\u2193Monocyte \u2192 Macrophage differentiation.<\/li>\n\n\n\n<li>\u2193Local inflammatory mediators (histamine, plasminogen activators, prostaglandins).<\/li>\n\n\n\n<li>Mild polycythemia in patients on high-dose glucocorticoids.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Central Nervous System and Eyes<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Behavioral Changes<\/strong>: Depression, euphoria, psychosis, apathy, lethargy possible with either deficiency or excess.<\/li>\n\n\n\n<li>Insomnia from increased neuroexcitability.<\/li>\n\n\n\n<li><strong>Glaucoma Risk<\/strong>: \u2191Intraocular pressure by \u2191aqueous humor production, \u2193drainage (matrix deposition in trabecular meshwork).<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Gastrointestinal Tract<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>\u2191Peptic ulcer risk from \u2191acid, \u2191pepsin, \u2193mucus in stomach.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Endocrine Effects<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Thyroid<\/strong>: \u2193TSH secretion, inhibits T4 \u2192 T3 (5\u2032 deiodinase).<\/li>\n\n\n\n<li><strong>Gonadal<\/strong>: \u2193GnRH pulsatility, \u2193LH\/FSH release \u2192 potential hypogonadism.<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>BIOSYNTHESIS AND METABOLISM OF ADRENAL CORTICAL HORMONES Overview of Adrenal Steroids ACTH Regulation and Diurnal Rhythm Synthesis Pathway of Cortical Steroids Cholesterol Sources and&hellip;<\/p>\n","protected":false},"featured_media":0,"template":"","oen_topic_chapter":[684],"class_list":["post-4422384","oen_topic","type-oen_topic","status-publish","hentry","oen_topic_chapter-adrenal-gland"],"_links":{"self":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422384","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic"}],"about":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/types\/oen_topic"}],"version-history":[{"count":5,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422384\/revisions"}],"predecessor-version":[{"id":4422825,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422384\/revisions\/4422825"}],"wp:attachment":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/media?parent=4422384"}],"wp:term":[{"taxonomy":"oen_topic_chapter","embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic_chapter?post=4422384"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}