Adrenal Gland 1 2024 PDF

Cellular Biology & Homeostasis ADRENAL GLAND - part 1 VP 2024 Clara Camargo, DVM 1. Describe the location of the adrenal glands and the microscopic structure (layers/zones) 2. List the hormones produced in each layer/zone 3. Define steroidogenesis and describe the transport of steroid hormones in th...

Cellular Biology & Homeostasis ADRENAL GLAND - part 1 VP 2024 Clara Camargo, DVM 1. Describe the location of the adrenal glands and the microscopic structure (layers/zones) 2. List the hormones produced in each layer/zone 3. Define steroidogenesis and describe the transport of steroid hormones in the blood 4. Understand the role of the HPA axis regulating steroidogenesis 5. Understand how steroid hormones trigger response in the target cells (hormone-receptor interaction) 6. Briefly describe the elimination of the steroid hormones and the clearance half-life 7. Describe the regulation of mineralocorticoids synthesis/secretion 8. Describe the effects of aldosterone on the kidney's distal tubules Located next to the cranial pole of the kidneys Main hormones of adrenal gland belong to 2 different families: Assist with maintaining homeostasis by: Steroid hormones (adrenal cortex)  Regulating body’s adaptive responses to stress*  Glucocorticoids (cortisol)  Maintenance of body balance of:  Mineralocorticoids  water  sodium  potassium  Control of blood pressure (aldosterone)  Androgens (sex hormones) Catecholamines (adrenal medulla)  Epinephrine  Norepinephrine Located next to the cranial pole of the kidneys Microanatomy organization Cortex Mesodermal in origin 3 layers (zones) Medulla Ectodermal in origin mineralocorticoids glucocorticoids androgens catecholamines ADRENOCORTEX CELL Hypothalamus CRH Adenohypophysis ACTH PKA  Derived from cholesterol Cholesterol is carried in blood plasma by LDLs Enters the cells via receptor mediated endocytosis → then is either used immediately or stored in vesicles (cholesterol ester)  In the first step, cholesterol is converted to pregnenolone This first step is common to all adrenocortical hormones Occurs in the mitochondria This step is regulated by ACTH (adenohypophysis)  Limits the rate of synthesis of all adrenocortical hormones FYI Clinical treatment example: ketoconazole can reversibly inhibit steroidogenesis, blocking several enzymes in different steps of the synthesis pathway → reduces mainly cortisol levels) Adrenal cortex produces→ steroid hormones ADRENAL CORTEX Different tissues of the adrenal gland (the different zones) express different enzymes  not all processes occur in all cells i.e., cells of the zona glomerulosa don’t have aromatase Steroid hormones are not stored in vesicles  When made, steroid hormones are secreted immediately by diffusion across the cell membrane (lipophilic) Hydrophobic → carried in plasma in association with transport proteins:  Corticosteroid-binding globulin (CBG) or transcortin  Albumin Cortisol transport Aldosterone transport 75% bound to transcortin 10% bound to transcortin 15% bound to albumin 50% bound to albumin 10% unbound (free state) 40% unbound (free state) transcortin Steroid hormones bind to intracellular receptors  steroid receptor superfamily steroid receptors can be located:  cytosol  nucleus cytoplasmic receptors translocate to the nucleus after hormone binding Androgen hormones can bind to cell surface receptors (GPCR, ligand-gated channels and others) triggering a rapid cellular response Hormones bind to their respective intracellular receptor → altering the ability of these proteins to control the transcription of specific genes Metabolism involves mainly the liver  Modification of the hormones for excretion  Conjugation to sulfates and glucuronides reduces biological potency become water-soluble for passage in the urine Clearance half-life  cortisol: 60 minutes  aldosterone: 20 minutes Mineralocorticoids are corticosteroids that influence salt and water balance  Electrolyte and fluid balance (mainly Na+ K+ and water)  Aldosterone is the primary mineralocorticoid What stimulates aldosterone synthesis and secretion?  Hypotension RAAS  ↓ [Na+]  ↑ [K+]  ACTH has little effect in aldosterone synthesis There are few receptors for ACTH located in the cells of zona glomerulosa Kidney glomerulus Production of aldosterone is mainly regulated by the Renin-angiotensin- aldosterone system (RAAS) STIMULI for renin secretion:  ↓ [Na+] in renal filtrate detected by cells of macula densa  Reduced blood pressure in the kidney detected by baroreceptors in the afferent arteriole  Sympathetic stimulation of the juxtaglomerular apparatus via β1 adrenoreceptors Nephron Zona glomerulosa – aldosterone regulation ⭣ [Na+] in filtrate ⭣ blood pressure [Na+] in filtrate water absorption blood pressure Potassium is another major regulatory factor for mineralocorticoid secretion  Increase in [K+] directly stimulates zona glomerulosa to secrete aldosterone → (independent of RAAS) ALDOSTERONE acts on distal tubules in the kidneys:  Active reabsorption of sodium (Na+) increasing activity of epithelial sodium channels synthesis of sodium-potassium pump (Na+/K+-ATPase)  Active secretion of potassium (K+) Synthesis of potassium channels Nephron  Active secretion of protons H+  Passive reabsorption of water (water flows with Na+) Sodium reabsorption (filtrate  blood): active process Potassium secretion (blood  filtrate): active process lumen (filtrate) → interstitial space → capillary: 2 steps