Transcript Cortisol
The Adrenal Glands Chapter 14 Adrenal gland The outer cortex (80%) releases steroids; the inner medulla (20%) releases catecholamines. Pyramid shape Adrenal gland No direct physical connection kidney Zona glomerulosa Cortex Zona fasciculata Zona reticularis Capsule Medulla fig 14-1, pg 434 Slide 2 Adrenal cortex Based on the arrangement of cells under a microscope, the adrenal cortex can be divided into three different zones. Glomerulosa = mineralocorticoids Fasciculata = glucocorticoids Reticularis = androgens Slide 3 Circadian rhythms Stress “Hypothalamicpituitary-adrenal axis” Hypothalamus CRH Anterior pituitary ACTH hypothalamus : CRH pituitary : ACTH adrenal cortex: promoting the growth of adrenal cortex, control of glucocorticoid Cortisol Adrenal cortex fig 14-3, pg 436 Slide 4 Three steroids are the primary products of the adrenal cortex. Cortisol (glucocorticoid), Aldosterone (mineralocorticoid) DHEA (weak androgen, converted to testosterone in peripheral tissue) Cortisol (glucocorticoid) Aldosterone (mineralocorticoid) Dehydroepiandrosterone (androgen) Slide 5 Cholesterol Pregnenolone Progesterone Zona glomerulosa Each cell makes steroids according to the enzymes it has. Corticosterone Aldosterone Cholesterol Pregnenolone 17-OH-Pregnenolone Zona fasciculata 17-OH-Progesterone “Steroid hormones are synthesized and secreted on demand and are not stored” Cortisol Cholesterol Pregnenolone Zona reticularis 17-OH-Pregnenolone Dehydroepiandrosterone fig 14-5, pg 437 Slide 6 Ratelimiting step; (LDL) thus is the primary site of regulation of steroid synthesis Slide 7 Control of Glucocorticoid Circadian rhythms Stress Cortisol is produced in the greatest amount in adrenal cortex Hypothalamus CRH Anterior pituitary ACTH Two type of stimuli 1. Circardian rhythm 2. Increased secretion in response to a variety of specific stimuli Cortisol Adrenal cortex fig 14-3, pg 436 Slide 8 Control of Glucocorticoid Circadian rhythms Stress Hypothalamus CRH Anterior pituitary ACTH Two type of stimuli 1. Circardian rhythm 2. Increased secretion in response to a variety of specific stimuli Cortisol Adrenal cortex fig 14-3, pg 436 Slide 9 Circadian rhythm of Glucocortcoids Sleep-wake pattern hypothalamic pituitary system CRH, ACTH, cortisol show circadian sleep-wake rhythm, with peak at awakening. Sleep Midnight AM Time of Day PM fig 14-7, pg 438 Slide 10 Stress-induced glucocorticoid secretion Slide 11 Negative feedback in glucocorticoid secretion Circadian rhythms Stress Hypothalamus CRH ACTH reduces CRH secretion Cortisol decreases the activity of CRHproducing neurons Anterior pituitary ACTH Cortisol Adrenal cortex Cortisol decrease the sensitivity of corticotropes to CRH fig 14-3, pg 436 Slide 12 Transport of Cortisol in the Blood - Corticosteroid-binding globulin (80%) - Albumin (15%) - Free active (5%) Slide 13 Physiological Effects of Glucocorticoids Cortisol enable us to survive the potentially damaging effects of wide fluctuation in environment as well as a lot of noxious factors Ex) even a modest fasting would not be possible without cortisol Slide 14 Physiological Effects of Glucocorticoids Cortisol nuclear receptors DNA altered transcription altered protein synthesis. Slide 15 Physiological Effects of Glucocorticoids Cortisol exerts its primary effects on three different tissues in the body 1) Liver 2) Skeletal muscle 3) Adipose tissue Slide 16 Cortisol accelerates liver urea cycle and amino acid conversion to glucose. Plasma Amino acids Liver Amino acid metabolizing Ammonia enzymes Gluconeogenesis Glucose Glycogen synthesis Urea cycle Urea Cortisol increases the activity of enzymes involved fig 14-8, pg 439 Slide 17 In muscle, cortisol decreases protein (1) decreases muscle protein synthesis; (2) increases degradation of protein and amino acid release. Plasma •Anabolic steroids ; increase muscle mass ; androgens (catabolic steroid) Cortisol Liver Amino acids Muscle protein Gluconeogenesis Cortisol Glucose synthesis Net transfer of amino acid Increased blood glucose fig 14-9, pg 440 Slide 18 Cortisol in Adipose Tissue - Cortisol decreases adipose glucose uptake (anti-insulin) and increases lipolysis. - differential sensitivity of adipose tissue: Hypersecretion of cortisol redistribution of the body fat Slide 19 Other effects of cortisol Permissive action: Cortisol enhances effect of other hormones, e.g., EPI stimulation of lipolysis in adipose tissue. Cortisol make vessels responsive : in the absence of cortisol, BP decreases dramatically. Cortisol increases RBCs, neutrophil and platelets. Slide 20 Phamacological effects of cortisol Cortisol has anti-inflammatory and immunosuppressive effects at pharmacological doses (much higher conc. than physiological amounts). So, glucocorticoid is used for treatment of asthma, or for suppressing the rejection response to transplanted organs. Slide 21 Control of Mineralocorticoids Decreased blood pressure in kidney renin Liver Angiotensinogen Kidney Renin proteolysis (granular Angiotensin I cell) 10 a.a. 8 a.a. Angiotensin II Lung Angiotensinconverting enzyme Angiotensin II stimulates aldosterone release. Zona glomerulosa cells Aldosterone fig 14-10, pg 442 Slide 22 Control of Mineralocorticoids Elevated extracellular K+ directly stimulates glomerulosa cells to release aldosterone. Aldosterone promotes K+ secrestion by the kidney and therefore lower the plasma K+ concentration. Slide 23 Effects of Mineralocorticoids Aldosterone stimulates Na+ (and hence water) retention by kidney and K+ loss. to increase in extracellular fluid volume Increase blood pressure Slide 24 Excess secretion of glucocorticoid (Cushing’s syndrome) thinner skin & red cheeks; lost connective tissue (protein loss) of the skin. Thin arms & legs ; loss of muscle mass by protein catabolism and fat redistributi on Redistribution of fat: Round face •hypertension •Diabetes •High susceptibility to infection •Impaired bone metabolism (bone fx, osteoporosis) Slide 25 Deficiency in steroid production in adrenal cortex (adrenal insufficiency) Primary adrenal insufficiency (Addison’s disease) has low cortisol and aldosterone; Secondary adrenal insufficiency (low ACTH) just lowers cortisol. Addison symptom: Electrolyte imbalance Hypotension (Na reduction and decreased vascular reactivity), Fatigue (Electrolyte imbalance), Hypoglycemia Skin pigmentation (high ACTH) Slide 26 Adrenal Medulla Is part of sympathetic nervous system, and is called sympathoadrenal Brain system Postganglionic sympathetic neuron Spinal cord Sympathetic ganglia Pass without synapsing in chain NE Preganglionic Sympathetic neurons Adrenal glands Medulla Blood Epinephrine Heart Various effector organs Adrenal chromaffin cells are analogous to sympathetic postganglionic neurons. fig 14-12, pg 445 Slide 27 Adrenal chromaffin cells functions as neuroendocrine cells. They influence the activity of a variety of effector organs throughout the body. Slide 28 Sympathetic n. Tyrosine + Tyrosine hydroxylase DOPA Rate-limiting Dopamine Cortisol from adrenal cortex Norepinephrine Chromaffin cells secrete epinephrine into the blood, instead of NE at a synapse. Input of sympathetic stimulation increases epi synthesis by increasing activity of tyrosine hydroxylase. + PNMT Epinephrine fig 14-13, pg 446 Slide 29 Epinephrine is packaged within chromaffin cells into vesicles known as chromaffin granules. Slide 30 EPI released into blood has same effects as sympathetic stimulation, but effects last longer. EPI increases heart rate and air flow, and shunts blood from skin and viscera to muscles. “Fight or Flight” bettering the chances of survival Slide 31 EPI raises glycogenolysis in liver/muscle and lipolysis in adipose; elevates blood glucose. Liver Glycogenolysis Glucose Lactate Glycerol Lactate Glycogenolysis Blood Glucose Fatty acids Lipolysis Adipose tissue Muscle Heart & skeletal m. fig 14-14, pg 448 Slide 32