{"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 Modifications Key Enzymes and Locations Pathway Details in Adrenal Cortex Normal Secretion Rates Metabolism of Cortisol and Aldosterone Cortisol Binding and Interconversion Aldosterone Metabolism BIOLOGIC ACTIONS OF CORTISOL Carbohydrate, Protein, 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","post-wrapper","thrv_wrapper"],"_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}]}}