Endocrine System :Endocrine System


The Classical Endocrine System :The Classical Endocrine System Pineal gland Hypothalamus / Pituitary Thyroid Parathyroid Thymus Adrenal glands Pancreas Gonads


Other Endocrine Organs :Other Endocrine Organs Stomach - releases gastrin from G-cells Duodenum – CCK, secretin Heart – ANP Kidney – renin, erythropoietin Placenta - hCG


Endocrine System Function :Endocrine System Function Maintenance of homeostasis through negative feedback loops


Endocrine System Function :Endocrine System Function Communication between organ systems within the body (like nervous system) Differs from the nervous system: changes take longer to occur and changes persist longer as well.


Endocrine System Function :Endocrine System Function Hormones are utilized as chemical messengers Messages are received by target cells


Hormones :Hormones Recall the distinction between exocrine and endocrine glands Exocrine: through a duct Endocrine: into the blood


Hormones :Hormones Endocrine hormones are transmitted in the bloodstream to all parts of the body Hormones only have an effect on those cells that have a hormone receptor embedded in the cell membrane (target cells) 2 types of endocrine hormones: steroid & non-steroid


Hormones :Hormones


Hormones :Hormones


Steroid Hormones :Steroid Hormones Slower, longer lasting effect than non-steroid hormones Derived form cholesterol Lipid soluble, need to be transported in the bloodstream combined with a transport protein


Steroid Hormones :Steroid Hormones Mainly from the adrenal cortex and/or gonads Mineralocoritcoid → aldosterone Glucocorticoids → cortisol, cortisone Sex steroids → progestin, estrogens, androgens


Non-steroid Hormones :Non-steroid Hormones Water soluble – most are transported freely in the blood Cascade of reactions within the cell “amplifies” the signal This type of hormone causes a more rapid onset and shorter duration of the effect than steroid hormones


Non-steroid Hormones :Non-steroid Hormones Types of Non-steroid hormones Protein (polypeptide) – insulin, growth hormone, FSH Glycoprotein – LH, TSH Oligopeptide – ADH, oxytocin Amine –norepinephrine, epinephrine, dopamine (neurotransmitters)


Paracrine Hormones :Paracrine Hormones Do not enter the general circulation Communication from cell to cell within a specific tissue Very low levels in the blood Have little or no effect in distant tissue Example: prostaglandins


Pituitary :Pituitary Interacts with many (not all) endocrine glands as part of a feedback loop between the hypothalamus and the respective gland.


Pituitary :Pituitary The pituitary serves as a link between the CNS (hypothalamus) and the rest of the endocrine system


Pituitary :Pituitary The pituitary is suspended from a stalk (infundibulum) attached to the hypothalamus and enclosed within the sella turcica (sphenoid bone)


Pituitary :Pituitary Actually 2 separate glands: anterior pituitary & posterior pituitary No blood brain barrier in the hypothalamus


Anterior Pituitary :Anterior Pituitary The releasing hormone is secreted into a portal system Cells in the anterior pituitary are stimulated to secrete another hormone


Posterior Pituitary :Posterior Pituitary Neurons from the hypothalamus enter the posterior pituitary and stimulate cells to secrete hormones


Anterior Pituitary :Anterior Pituitary Note: GH is also called somatotropin There are also inhibitory factors from the hypothalamus for GH and PRL


Posterior Pituitary :Posterior Pituitary * failure of the posterior pituitary to secrete ADH results in Diabetes Insipidus (DI)……if no ADH is produced the result is production of LARGE volumes of dilute urine


Growth Hormone :Growth Hormone GHRH/somatostatin  GH or somatotropin  cells related to body growth Produced in the ant. Pituitary Secretion declines gradually with age Many more GH producing cells in ant. pituitary than any other type


Growth Hormone :Growth Hormone Increased cell division (mitosis) & increased cell growth & differentiation The main effects are on cartilage, muscle, bone, fat Promotes protein synthesis (transcription/translation) Anti-insulin effect - elevates blood sugar


Growth Hormone :Growth Hormone Catabolism of fat for energy instead of glucose Muscle & bone are effected indirectly through Insulin like Growth Factor (IGF-1) increased muscle mass, bone lengthening and decreased fat tissue


Growth Hormone :Growth Hormone Continued secretion of high levels after epiphysial plate closure is called acromegaly Bones continue to thicken even after epiphysial plate closure


Growth Hormone :Growth Hormone Acromegaly is usually related to a pituitary tumor


Prolactin :Prolactin More PRF/and less PIF from the hypothalamus Causes PRL secretion from the ant. Pituitary Effects the mammary gland in women/testes in men


Prolactin :Prolactin In women increased levels during pregnancy after delivery causes mammary glands to produce milk In men increases sensitivity to LH and indirectly enhances testosterone production


Thyroid Gland :Thyroid Gland TRH (hypothalamus) → TSH (pituitary) → Thyroid hormone (Thyroid gland)


Thyroid Gland :Thyroid Gland 2 lobes, on either side of the trachea, connected by an isthmus


Thyroid Gland :Thyroid Gland Microscopic anatomy Thyroid follicles, lined by secretory epithelium (follicular cells) Filled with thyroglobulin (transport protein) Parafollicular cells between the follicles


Thyroid Function :Thyroid Function Secretes two hormones (both require iodine as a precursor) Thyroxine (T4) & Triiodothyronine (T3)


Thyroid Function :Thyroid Function (T4): 90% of all Thyroid hormone Less active Converted to T3 in the cell Most remains in the bloodstream as reservoir of thyroid hormone


Thyroid Function :Thyroid Function (T3): 5 times more metabolically active, but only 10% of total hormone that is produced


Thyroid Function :Thyroid Function Mitochondria: increased cellular respiration Ribosomes: increased protein synthesis Chromatin: increased transcription DNA to mRNA Binds to three sites in the cell


Hyperthyroidism :Hyperthyroidism Thyroid hormones promote cellular respiration Cellular respiration requires oxygen, therefore heart rate & respiratory rate are increased Produces heat; causes sweating Higher metabolic rate requires more calories, which is a stimulus for hunger


Graves Disease :Graves Disease The most common form of hyperthyroidism (autoimmune) Signs and symptoms may include heat intolerance,  appetite, weight loss, warm moist skin, nervousness, tremor,  BP, tachycardia, goiter, exophthalmos Exophthalmos may be due to an autoimmune, inflammatory reaction in the soft tissue that is confined within the boney orbit


Endemic Goiter :Endemic Goiter A goiter is an enlarged thyroid gland Endemic goiter is due to lack of iodine in the diet No thyroid hormone is produced so there is no negative feedback The thyroid gland hypertrophies as it “tries” to make more thyroid hormone


Hypothyroidism :Hypothyroidism In children (cretinism) permanent mental retardation due to inadequate nervous system development In adults common cause of fatigue other symptoms are related to low BMR cold intolerance, weight gain,  CNS function (mentation), BP, dry skin


Adrenal Glands :Adrenal Glands Each gland is actually 2 separate glands: the cortex & medulla


Adrenal Functions :Adrenal Functions


Adrenal Medulla :Adrenal Medulla Secretes Catecholamines (Epinephrine & Norepinephrine) Derived from SNS neurons (Chromaffin cells) that lack dendrites & axons


Adrenal Medulla :Adrenal Medulla Innervated by SNS Secretes SNS neurotransmitters mostly Epinephrine (Adrenalin) The presence of these neurotransmitters in the circulation lowers the threshold for transmission of an impulse in the SNS for about 30 min.


Epinephrine :Epinephrine Elevates blood sugar – glucose sparing effects to preserve glucose for the CNS glycogenolysis gluconeogenesis


Adrenal Cortex :Adrenal Cortex 3 layers


Adrenal Cortex :Adrenal Cortex


Slide 49:Aldosterone – Na+ retention/ K+ secretion Water follows Sodium, so fluid volume and BP increase too Recall that aldosterone secretion can be promoted by: ACTH Angiotensin II Low Na+ High K+ Adrenal Cortex: Z. Glomerulosa


Slide 50:Secretes Cortisol (hydrocortisone) Corticosterone and cortisone are two other similar hormones that are secreted Steroid medication can suppress adrenal function Adrenal Cortex: Z. Fasciculata


Slide 51:Two basic effects of Cortisol: Glucose sparing effects: increased glucose synthesis & protein/lipid catabolism (gluconeogenesis) Anti-inflammatory effects: inhibits WBC function, decreased phagocytosis, decreased chemotaxis, decreased mast cell degranulation Adrenal Cortex: Z. Fasciculata


Adrenal Cortex: Z. Reticularis :Adrenal Cortex: Z. Reticularis Sex steroids – small amount of estrogens & weak androgens (DHEA), which is a precursor of testosterone Testosterone is required in men & women – pubic & axillary hair, libido, apocrine sweat glands most testosterone is produced in testes in men 50% produced by the adrenal gland in women


Cushing’s Disease :Cushing’s Disease Hyperfunction of the Adrenal glands Disrupts normal carbohydrate & protein metabolism (Cortisol) characteristic lipid deposits in the face Potential electrolyte imbalance (Aldosterone) Mood changes (Testosterone)


Gonads :Gonads Ovaries Secrete estrogen & progesterone during the menstrual cycle FSH from the pituitary causes maturation of the follicle & egg LH causes ovulation (rupture of the follicle – release of the egg) Testes FSH promotes spermatogenesis LH causes interstitial cells to secrete testosterone Testosterone from adrenal gland is also present in women, but at much lower levels Produces secondary sexual characteristics in men


Parathyroid Glands :Parathyroid Glands Not linked to the hypothalamic-pituitary axis 4 small nodules of tissue in the thyroid gland


Parathyroid Glands :Parathyroid Glands PTH is secreted in response to low serum Ca++ (hypocalcemia) Promotes synthesis of calcitrol (active metabolite of vitamin D), which ↑ GI absorption of Ca++ Limits Ca++ secretion by the kidney Stimulates osteoclasts to reabsorb bone


Slide 57:PTH is opposed by the action of calcitonin Secreted in response to elevated Ca++ (hypercalcemia) by parafollicular (C-cells) of the thyroid gland Little effect in adults Stimulates mineral deposition in bone by osteoblasts Parathyroid Glands


Pancreas :Pancreas Not linked to hypothalamic pituitary axis Both exocrine & endocrine functions


Pancreas :Pancreas Endocrine hormones: insulin & glucagon secreted by cells in the islets of Langerhans


Glucagon :Glucagon Alpha cells secrete glucagon Glucagon is secreted in response to low blood sugar, causing glycogen to be converted to glucose (glycogenolysis)


Insulin :Insulin Beta cells secrete insulin insulin is secreted in response to ↑ blood sugar, causes ↑ permeability of cell membranes throughout the body to glucose Except CNS...does not require insulin to take up glucose


Diabetes Mellitus :Diabetes Mellitus Elevated blood sugar Normal fasting blood sugar is 70 – 100 mg/dL 100 – 125 mg/dL is “prediabetic” Higher than 125 mg/dL is either Type I or Type II diabetes


Type I Diabetes Mellitus :Type I Diabetes Mellitus A failure of beta cells to produce insulin Also called IDDM (Insulin Dependent DM) complete loss of insulin means that replacement is required Usually onset is in childhood (juvenile onset)


Type I Diabetes Mellitus :Type I Diabetes Mellitus Abrupt onset of symptoms DKA (diabetic ketoacidosis) No glucose is available to cells They utilize lipids instead This produces ketoacids (lower the pH) Polydipsia (thirst) Polyphagia (hunger) Polyuria (osmotic diuresis)


Slide 65:The renal threshold for glucose resorption is exceeded resulting in glycosuria Poorly controlled DM is a disease of small blood vessels diabetic nephropathy diabetic retinopathy diabetic neuropathy changes in coronary & peripheral vessels increase the risk of vascular disease Type I Diabetes Mellitus


Diabetes Mellitus type II :Diabetes Mellitus type II An insensitivity of an insulin receptor in cell membranes to insulin NIDDM (Non Insulin Dependent DM) usually does not require insulin (oral hypoglycemics) Usually onset is as an adult Onset is insidious Usually no ketoacidosis


Diabetes Mellitus :Diabetes Mellitus Long term monitoring of blood sugar levels (months) Hgb A1C (glycosylated hemoglobin) A type of hgb that incorporates a sugar molecule More Hgb A1C is made when blood sugar levels are high


Pineal gland :Pineal gland The main hormone is melatonin The precursor is a CNS neurotransmitter, serotonin


Pineal gland :Pineal gland Production and secretion of melatonin is stimulated by darkness Information about light levels is provided through the retina in mammals


Pineal gland :Pineal gland Circadian rhythm Regulates sleep / wake cycle Undergoes involution during childhood, which may bring about the onset of puberty Near the skin in non-mammal vertebrates Light levels are perceived directly Regulates seasonal behavior in other animals Migratory patterns in birds Breeding cycles in animals with seasonal reproductive patterns


Thymus :Thymus Posterior to the sternum Larger in adolescence Regresses at puberty Secretes thymosin


Thymus :Thymus Thymosin causes undifferentiated lymphocytes to become T cells Blood – thymus barrier in the cortex Only T cells that are “self tolerant” are released to the medulla and into the rest of the body cortex medulla


Stress :Stress A stressor is a stimulus to promote a response to a threatening situation


Stress :Stress 3 phases of the stress response The alarm phase Resistance phase: occurs as glycogen is consumed Exhaustion phase: chronic stress occurs over a period of weeks


Slide 75:An immediate response Increased sympathetic output (fight or flight) The adrenal medulla secretes catecholamines like adrenalin (SNS neurotransmitter) Stress: The Alarm Phase


Slide 76:SNS input to the kidney initiates the RAA cascade which leads to : Increased BP to supply large skeletal muscles Increased fluid retention to compensate for potential fluid loss through sweat or hemorrhage Glycogen stores are consumed in a few hours Stress: The Alarm Phase


Slide 77:Occurs as glycogen is consumed: Hypothalamus → CRH → ACTH → Cortisol Stress: The Resistance Phase


Slide 78:Cortisol decreases glucose use peripherally (glucose sparing for the CNS) Promotes the breakdown of protein & fatty acids, which are converted to glucose in the liver (gluconeogenesis) Stress: The Resistance Phase


Slide 79:Both Adrenaline (alarm phase) and Cortisol (resistance phase) elevate blood sugar Stress and Blood Sugar


Stress: The Exhaustion Phase :Stress: The Exhaustion Phase Chronic stress occurs over a period of weeks: Less protein is available for immune system function (gluconeogenesis) ↓ ability to make antibodies (protein) ↑ susceptibility to infections ↓ protein available for wound healing


Paracrine Secretions :Paracrine Secretions Paracrine hormones exert a local effect Eicosanoids are paracrine secretions They are produced by the Arachidonic acid pathway


Slide 82:Arachidonic acid (a fatty acid) is produced from phospholipids in the cell membrane This reaction is catalyzed by phospholipase A2 Arachidonic Acid Pathway


Slide 83:Arachidonic acid is then subjected to either of two metabolic pathways lipoxygenase – leads to the production of leukotrienes, chemical mediators of inflammation Arachidonic Acid Pathway


Slide 84:cyclooxygenase – leads to the production of prostaglandins, thromboxane, and prostacyclin Arachidonic Acid Pathway


Paracrine Secretions :Paracrine Secretions Thromboxane is secreted by platelets to enhance platelet aggregation Prostaglandins have many effects depending upon the specific metabolite fever pain etc.


Paracrine Secretions :Paracrine Secretions Steroid medication (e.g. cortisol/prednisone) blocks the production of arachidonic acid (phosphlipase) *Non-steroidal anti-inflammatories (NSAID’s) like aspirin and Ibuprofen block the cyclooxygenase pathway to reduce inflammation & fever