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USC BISC 307L - Adrenal Glucocorticoids
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GlucocorticoidsSlide 1- Anatomy of the Adrenal GlandThe adrenal cortexTop of kidneys1. Outer cortex –what were focusing on1. Zona glomerulosasecretes mineralocorticoids (aldosterone)aldosterones main target is kidney tubule and facilitates Na+ reabsorption and K+ secretion and does the same thing in large intestine2. Zona fasciculatesecretes glucocorticoidssomething to do with regulating glucosemain subject of this lecture3.Zona reticularissecretes androgensnot very important in menbut important source of sex steroid hormones in women after menopause (only source of sex hormones)2. Inner medullasynthesizes catecholaminesSteroid Hormone Synthesisdon’t need to memorize but be familiar with take home messagePathway of synthesis of steroid hormonesMain messages:1. All of these steroid hormones are synthesized by cholesterol2. All interrelated structurally3. Many of the important ones are actually related to the others as precursors or products to the othersAll of these substances are highly regulated because powerful hormonesHighly lipid soluble and water insoluble so can't be synthesized in advance and stored in vesicles so they are synthesized on demand by mitochondria and take offDiffuse bound to carrier proteins- specific and non specific carrier proteinsCorticosteroid binding globulin and transcortin are carrier proteins for cortisol and corticosteroneControl of Cortisol Secretionhow secretion of cortisol is controlledfar right cortisol being secreted by adrenal cortex under direct control of ACTH secreted by the anterior pituitary(stimulates growth and hormone synthesis of adrenal gland because tropic- release of ACTH which is controlled by hypothalamic hormones released into portal vein of anterior pituitary (main releasing hormone is CRH but there is another one, ADH, that is a releasing hormone) which brings us back to the hypothalamus. Secretion by hypothalamus is controlled by many different factors:1. diurnal rhythm-highest levels of cortisol is just before you wake up and then declines2. Feeding3. Anxietythinking about stress4. NeurotransmittersSympathetic activation stimulates this systemParasympathetic inhibits this system5. StressVERY IMPORTANTThe most powerful influence on the hypothalamus to control this system is stress of any sort (starvation, tissue trauma, infection, extreme temperature, restraint)6. Lymphokinesclass of cytokines in immune systems that lymphocytes use and they mainly inhibit this whole system (reduce levels of cortisol)where the immune system endocrine system and nervous system are “talking” to each othera vein with capillaries at both end is a portal vein (form hypothalamus anterior pituitary is one of the only ones in the body- called hypothalamichypophyseal portal vein)inhibition: the dashed lines show that ACTH feeds back and inhibits the secretion of CRH and the steroid cortisol feeds back and inhibits the secretion of ACTH from the anterior pit and secretion of CRH as wellPathology of Adrenal CortexHow the adrenal gland controls and how it is affectedPerson in middle has normal appearing adrenal cortexCushing’s diseaseAdrenal cortex is hypertrophied due to a primary tumor in the cells that secrete ACTH and secrete ACTH like crazyTop: administered cortisol in unnatural formsCortisol has an affect in suppressing the immune system (inflammation and pain)Used to relieve pain (joint problems) but the course and time of therapy must be limited because if prolonged it will inhibit ACTH and CRH secretion resulting in atrophy which is NOT EASILY REVERSEDGreatly increased risk of infection or cancerDoesn’t take much to get in trouble like thisEffects of Cortisol1. Stimulates gluconeogenesis (from AAs) in liverone of the strongest direct affects of cortisolsynthesis of glucose from non carbs in liver cellsincreasing transcription of all the transporters that are needed to break down and convert amino acidsglucose produced is stored as glycogen in these liver cells- so cortisol stimulates the enzyme for glycogen stimulus2. Stimulates glycogen synthesis in liver3. Stimulates protein catabolism, especially in musclewhere the amino acids will come from4. Inhibits protein synthesis in most cells5. But, increases protein synthesis in liver6. Stimulates lipolysis in adipose tissuetriglycerides and fat tissues are broken down to glycerol and free fatty acids7. Opposes the action of insulinmakes sense because cortisol is making more glucose for the bloodNet effects: Protein in muscle is converted toglycogen in liver increase blood glucoseIndirect effects: via glucagon(hyperglycemic effects reinforced by cortisol), growth hormone(cortisol increases these lipolytic effects), epinephrine (cortisol increases stimulation of glycogen in liver to raise plasma glucose)Generally: hyperglycemic, lipolytic, and ketogenic catabolic in general- cause tissues to break down (these are all things that happen with stress)Role of Cortisol1. Defends against hypoglycemia caused by insulinhypoglycemia is potentially fatal especially for brain because brain needs glucose2. Long term buildup of glycogen stores so that catecholamines (epi from adrenal medulla and norepi from sympathetic nerves) can cause short-term releaseimportant for maintaining liver glycogen which is a vital source of glucose to be drawn upon during emergency situations.3. Mobilize energy stores during fasting and starvationfrom maintaining liver glycogencortisol main hormone to keep you living during true starvationOther Effects of Cotrisol1. Anti-inflammatorydecrease synthesis of arachidonic acidtherefore decrease synthesis of eicosanoid paracrinesthese are all mediators of inflammation and pain (why cortisol is used in pain suppression)2. Immunosuppressantdecrease cytokine releasedecrease antibody productiondecrease leukocyte activity3. Ca2+ loss from bodybone demineralizationincrease renal Ca2+ excretiondecrease intestinal Ca2+ absorption4. Effects on brainmood changesmemory and learning-suppresses itbut improves memory and learning of stressful eventsBISC 307L 1st Edition Lecture 16 Current Lecture Glucocorticoids- Slide 1- Anatomy of the Adrenal Glandoo The adrenal cortex Top of kidneys 1. Outer cortex –what were focusing on 1. Zona glomerulosa- secretes mineralocorticoids (aldosterone)o aldosterones main target is kidney tubule and facilitates Na+ reabsorption and K+ secretion and does the same thing in large intestine 2. Zona fasciculate- secretes


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