Adrenal Gland.docx
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Adrenal Gland: General Info Located at cranial poles of kidneys Maintains homeostasis by: regulating adaptive response to stress balancing water, sodium, potassium controlling blood pressure Main hormone families: catecholamines: epinephrine, norepinephrine produced in: adrenal medulla (ectodermal o...
Adrenal Gland: General Info Located at cranial poles of kidneys Maintains homeostasis by: regulating adaptive response to stress balancing water, sodium, potassium controlling blood pressure Main hormone families: catecholamines: epinephrine, norepinephrine produced in: adrenal medulla (ectodermal origin) steroid hormones: glucocorticoid (cortisol), androgen (sex hormones), mineralocorticoids (aldosterone) produced in: adrenal cortex (mesodermal origin with 3 layers) Adrenal Gland Divisions (in order of external to internal of the gland) Cortex Region Zona glomerulosa: produce mineralocorticoids Zona fasciculata: produce glucocorticoids Zona reticularis: produce androgens Medulla Region Adrenal medulla: produce catecholamines Steroidogenesis (steroid hormone synthesis) Step 1: cholesterol travels in blood using LDL Step 2: cholesterol enters cell via receptor mediated endocytosis Step 3: cholesterol is either used immediately or stored in vesicles called “cholesterol ester” Step 4: cholesterol is converted into pregnenolone within the mitochondria (this happens in all adrenocortical hormones) ACTH which is produced by the adenohypophysis regulates this step which limits rate of adrenocortical hormone synthesis Steroid hormones are not stored and must be used immediately or secreted by diffusion across the cell membrane (because they are lipophilic) Steroid hormone transport They are hydrophobic so they require a transport protein Transport protein options: Corticoid binding globulin (AKA: CBG or Transcortin) Albumin Cortisol transport 75% use transcortin 15% use albumin 10% are unbound (in a free state) Aldosterone transport 10% use transcortin 50% use albumin 40% are unbound (in a free state) The free state is necessary because it is the only state that can enter the target cell Total cortisol= free cortisol concentration + bound cortisol concentration Hormone-Receptor Interactions Steroids bind to intracellular receptors (either within the nucleus or cytosol) Cytosol receptors translocate to nucleus after hormone binding Androgens bind to cell surface receptors, allowing for a more rapid cellular response. These receptors can be GPCR’s or ligand-gated channels, or another type Hormone-receptor binding alters ability of protein to control transcription of specific genes Zona glomerulosa: Mineralocorticoids Mineralocorticoids are corticosteroids influencing salt and water balance. This results in electrolyte and fluid balance (with water, sodiunm, and potassium) Aldosterone= primary corticosteroid Aldosterone synthesis is stimulated by hypotension, low sodium levels, and high potassium levels. However, it is not really impacted by ACTH, despite ATCH also having some receptors in the zona glomerulosa Steroid hormone metabolism Mainly happens within the liver The steroid is modified for excretion via conjugation to glucuronide and sulfate. This allows for water solubility to pass through urine and decreases biological potency Clearance half life: Aldosterone: 20mins Cortisol: 60mins Aldosterone regulation Renin angiotensin aldosterone system (RAAS) regulates aldosterone production Renin secretion is stimulated by: Macula densa detecting low sodium concentration in renal filtrate Baroreceptors in the afferent arterioles detecting low blood pressure in the kidneys Sympathetic stimulation of juxtaglomerular apparatus via beta 1 adrenoreceptors Potassium regulates mineralocorticoid secretion High potassium concentration stimulates zona glomerulosa to secrete aldosterone (works independent of RAAS) High potassium levels are also known as “hyperkalemia” RAAS: General Info Low sodium concentrations in filtrate, and low blood pressure stimulate renin secretion High sodium concentrations in filtrate, high water absorption, and high blood pressure will inhibit renin secretion ACE inhibitors will decrease blood pressure ADH will increase water being retained RAAS: Pathway Step 1: liver secretes angiotensinogen, and kidneys secrete renin Step 2: renin stimulates the conversion of angiotensinogen to angiotensin 1 Step 3: lung (pulmonary) and kidney (renal) endothelium surfaces produce ACE (angiotensin converting enzyme) Step 4: ACE stimulates conversion of angiotensin 1 to angiotensin 2 RAAS: Angiotensin 2 stimulation possibilities Stimulate adrenal gland cortex to secrete aldosterone. This can cause aldosterone to stimulate tubular NaCl reabsorption, potassium excretion, and water reabsorption. Angiotensin 2 can also directly cause this to happen Stimulate sympathetic activity Stimulate arteriole constriction and increasing blood pressure Stimulate neurohypophysis to secrete ADH Secreting ADH stimulates collecting ducts to reabsorb water Aldosterone’s Actions on the Kidney’s Distal Tubules: General Info Active reabsorption of sodium Increases activity of epithelial sodium channels Synthesizes sodium-potassium pumps Active secretion of potassium Synthesizes potassium channels Active secretion of protons (H+) Passive reabsorption of water Aldosterone’s Actions on the Kidney’s Distal Tubules: Pathway Step 1: aldosterone binds to cytoplasmic receptors Step 2: this stimulates transcription within the nucleus Step 3: new protein channes and pumps are synthesizes (made) Step 4: aldosterone inducing proteins modify existing proteins Step 5: this triggers increased sodium reabsorption into the blood, and potassium secretion into he lumen of the distal tubule (AKA: filtrate) Sodium: goes from filtrate to the blood (active process) Potassium: goes from blood to filtrate (active process)
