BISC 307L 1st Edition Lecture 16 Current Lecture Glucocorticoids Slide 1 Anatomy of the Adrenal Gland o o 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 glucocorticoids o something to do with regulating glucose o main subject of this lecture 3 Zona reticularis secretes androgens o not very important in men o but important source of sex steroid hormones in women after menopause only source of sex hormones 2 Inner medulla synthesizes catecholamines Steroid Hormone Synthesis o don t need to memorize but be familiar with take home message o Pathway of synthesis of steroid hormones o Main messages 1 All of these steroid hormones are synthesized by cholesterol 2 All interrelated structurally 3 Many of the important ones are actually related to the others as precursors or products to the others o All of these substances are highly regulated because powerful hormones o Highly 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 of o Difuse bound to carrier proteins specific and non specific carrier proteins o Corticosteroid binding globulin and transcortin are carrier proteins for cortisol and corticosterone Control of Cortisol Secretion o o how secretion of cortisol is controlled far 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 diferent factors 1 diurnal rhythm highest levels of cortisol is just before you wake up and then declines 2 Feeding 3 Anxiety thinking about stress 4 Neurotransmitters Sympathetic activation stimulates this system Parasympathetic inhibits this system 5 Stress VERY IMPORTANT The most powerful influence on the hypothalamus to control this system is stress of any sort starvation tissue trauma infection extreme temperature restraint 6 Lymphokines class 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 other a vein with capillaries at both end is a portal vein form hypothalamus anterior pituitary is one of the only ones in the bodycalled 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 well Pathology of Adrenal Cortex o o How the adrenal gland controls and how it is afected o Person in middle has normal appearing adrenal cortex o Cushing s disease Adrenal cortex is hypertrophied due to a primary tumor in the cells that secrete ACTH and secrete ACTH like crazy o Top administered cortisol in unnatural forms Cortisol has an afect 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 REVERSED Greatly increased risk of infection or cancer Doesn t take much to get in trouble like this Effects of Cortisol o 1 Stimulates gluconeogenesis from AAs in liver one of the strongest direct afects of cortisol synthesis of glucose from non carbs in liver cells increasing transcription of all the transporters that are needed to break down and convert amino acids glucose produced is stored as glycogen in these liver cells so cortisol stimulates the enzyme for glycogen stimulus o 2 Stimulates glycogen synthesis in liver o 3 Stimulates protein catabolism especially in muscle where the amino acids will come from o 4 Inhibits protein synthesis in most cells o 5 But increases protein synthesis in liver o 6 Stimulates lipolysis in adipose tissue triglycerides and fat tissues are broken down to glycerol and free fatty acids o 7 Opposes the action of insulin makes sense because cortisol is making more glucose for the blood o Net effects Protein in muscle is converted to glycogen in liver increase blood glucose o Indirect effects via glucagon hyperglycemic efects reinforced by cortisol growth hormone cortisol increases these lipolytic efects epinephrine cortisol increases stimulation of glycogen in liver to raise plasma glucose o Generally hyperglycemic lipolytic and ketogenic catabolic in general cause tissues to break down these are all things that happen with stress Role of Cortisol o 1 Defends against hypoglycemia caused by insulin hypoglycemia is potentially fatal especially for brain because brain needs glucose o 2 Long term buildup of glycogen stores so that catecholamines epi from adrenal medulla and norepi from sympathetic nerves can cause short term release important for maintaining liver glycogen which is a vital source of glucose to be drawn upon during emergency situations o 3 Mobilize energy stores during fasting and starvation from maintaining liver glycogen cortisol main hormone to keep you living during true starvation Other Effects of Cotrisol o 1 Anti inflammatory decrease synthesis of arachidonic acid therefore decrease synthesis of eicosanoid paracrines these are all mediators of inflammation and pain why cortisol is used in pain suppression o 2 Immunosuppressant decrease cytokine release decrease antibody production decrease leukocyte activity o 3 Ca2 loss from body bone demineralization increase renal Ca2 excretion decrease intestinal Ca2 absorption o 4 Efects on brain mood changes memory and learning suppresses it but improves memory and learning of stressful events