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174 Cards in this Set
- Front
- Back
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internal secretion
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ENDOCRINE
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substanced released into internal environment of body
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HORMONE OR ENDOCRINE REGULATORY MOLECULE
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internal environment of the body
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ECF
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whatever occurs to increase the amount of hormone in circulation
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SECRETION
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polar hormone examples
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AMINE HORMONES, PEPTIDE HORMONES
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3 major amine hormones
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DOPAMINE, NOREPINEPHRINE, EPINEPHRINE
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dopamine, norepinephrine, epinephrine collective term
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CATECHOLAMINES
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where are peptide hormones synthesized
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RER
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peptide horomes are first synthesized as...
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a part of a larger preprohormone
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what happens to a preprohormone
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cleavage of the signal sequence in the RER to form a prohormone
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what happens to a prohormone
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further processed in Golgi and secretory vessicles
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prohormone that gives rise to ACTH and alpha-MSH
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pro-opiomelanocortin (POMC)
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POMC gives rise to...
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ACTH and alpha-MSH
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where are polar hormones stored
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secretion vessicles
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how are polar horomes secreted
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by exocytosis
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how do polar hormones signal at their targets
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via cell surface receptors
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examples of nonpolar hormones
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steroid hormones and thyroid hormones
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the large protein precursor that leads to synthesis of thyroid hormones
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thyroglobulin
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hormone secretion is regulated by
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hormone synthesis
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peptide hormone whose binding to a receptor on the endocrine cell regulates hormone synthesis
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tropic hormone
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examples of carrier proteins that carry nonpolar hormones in circulation
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albumin or specific hormone binding proteins
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hormone dissolved in plasma
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free hormone
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method for bound nonpolar proteins to get into cell
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receptor-mediated endocytosis
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once inside cell, nonpolar hormones...
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signal via intracellular receptors that bind to DNA leading to transcription factors
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majority of thyroid hormone produced
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T4
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active form of thyroid hormone
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T3
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referring to fluid of the body (ECF)
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humoral
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hormones regulated humorally that uses a negative feedback loop to stablize and maintain the concentration of a substance
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homeostatic regulation (endocrine cell acts as sensor)
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How is PTH regulated
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humoral regulation
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hormone that functions in calcium homeostasis
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PTH
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why is Ca++ so regulated in the ECF
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Because of its effects on voltage-gated ion channels
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symptoms: ECF Ca++ too low, voltage-gated channels open spontaneously, hyperactivity of nerve and muscle cells = painful muscle spasms
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hypocalcemic tetany
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stimulus for PTH secretion
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hypocalcemia (low blood Ca++)
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3 specific actions of PTH
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1. stimulate the release of Ca++ from bone by stimulating bone resorption
2. stimulates Ca++ reabsorption in kidney to decease amount of Ca++ excreted in urine 3. indirectly promotes Ca++ absorption by the digestive tract |
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how does PTH indirectly promote Ca++ absorption by the digestive tract
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activating the enzyme in kidney cells that produces the active form of Vit D
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sensor on the parathyroid gland cell that detects changes in ECF calcium concentration
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calcium receptor
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make-up of calcium receptor
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7 transmembrane domain receptor that is coupled to a trimeric G protein
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What does the calcium receptor do when calcium levels are high
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when ECF calcium is high, calcium binds to the receptor and inhibits PTH secretion
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drugs that act as calcium receptor agonists to affect PTH secretion are called
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calcimimetics
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calcimimetic that has been approved to treat hyperparathyroidism
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cinacalcet
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what type of drug would be useful to treat hypoparathyroidism
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a calcium receptor agonist (calcilytic) - a drug that binds to the calcium receptor but does not active signal transduction
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2 examples of humorally regulated hormones
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INSULIN, PTH
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What state does insulin shift the body cells into?
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ABSORPTIVE STATE
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The state following the ingestion of a meal when nutrients are being absorbed and are abundant in the plasma
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ABSORPTIVE STATE
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2 storage molecules synthesized in response to insulin
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GLYCOGEN, TRIACYLGLYCEROL
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What cells produce glycogen?
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SKELETAL MUSCLE, LIVER
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What cells produce triacylglycerol?
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ADIPOCYTES, LIVER
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What happens to triacylglycerol that leaves the liver in response to insulin?
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EXPORTED TO ADIPOSE TISSUE IN PARTICLES OF VERY LOW DENSITY LIPOPROTEIN (VLDL)
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Most important stimulator of insulin secretion
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CONCENTRATION OF GLUCOSE IN BLOOD PLASMA
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What types of cells sense the concentration of glucose in the blood plasma?
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PANCREATIC BETA CELLS
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How does glucose enter a pancreatic beta cell?
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THROUGH A GLUCOSE TRANSPORTER
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What does metabolism of glucose in pancreatic beta cells lead to?
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METABOLISM OF GLUCOSE LEADS TO GENERATION OF ATP WHICH ACTS AS A LIGAND FOR LIGAND-GATED POTASSIUM CHANNEL --- CLOSES POTASSIUM CHANNEL WHICH LEADS TO DEPOLARIZATION OF THE CELL --- DEPOLARIZATION OPENS VOLTAGE GATED CALCIUM CHANNELS --- CALCIUM ENTERS THE CELL AND CAUSES EXOCYTOSIS OF SECRETORY VESSICLES CONTAINING INSULIN
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The potassium channel is a therapy target for what type of Diabetes?
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TYPE 2 DIABETES MELLITUS
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What is Type 2 Diabetes characterized by?
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INSULIN RESISTANCE
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2 drugs that enhance insulin secretion by binding to and closing potassium channels for which ATP is the normal ligand
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SULFONYLUREAS, MEGLITINIDES
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What is Type 1 Diabetes characterized by?
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ABSOLUTE INSULIN DEFICIENCY
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What is absolute insulin deficiency caused by?
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AUTOIMMUNE DESTRUCTION OF PANCREATIC BETA CELLS
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For PTH secretion, what protein acts as a sensor to detect changes in the regulated variable?
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CALCIUM RECEPTOR
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What sort of protein is stablized by extracellular calcium ions?
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VOLTAGE-GATED ION CHANNEL
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Hormones that work to increase insulin secretion
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INCRETINS
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Why is more insulin secreted in response to oral glucose than intravenous glucose?
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THE DIGESTIVE TRACT ACTIVATES A FEEDFORWARD MECHANISM THAT INCREASES INSULIN SECRETION ANTICIPATING A RISE IN BLOOD GLUCOSE AFTER A MEAL
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2 main incretin hormones
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GIP, GLP-1
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Where are GIP and GLP-1 secreted?
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ENDOCRINE CELLS IN THE EPITHELIUM OF THE SMALL INTESTINE
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What stimulates incretin release?
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GLUCOSE IN THE SMALL INTESTINE
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What do incretins target?
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STIMULATE PANCREATIC BETA CELLS TO SECRETE MORE INSULIN IN RESPONSE TO THE SAME AMOUNT OF BLOOD GLUCOSE
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3 reasons why incretin based thereapies might be effective for T2DM
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-DEFECTIVE INCRETIN ACTION
-GLUCOSE DEPENDENT EFFECT ON INSULIN SECRETION -OTHER EFFECTS OF GLP-1 BENEFICIAL |
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How is incretin action defective in T2DM?
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LESS GLP-1 SECRETION AND BETA CELLS LESS RESPONSIVE TO GIP
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Other than glucose dependent stimulation of insulin, how might GLP-1 help T2DM?
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-INHIBITING GLUCAGON SECRETION
-DELAYS STOMACH EMPTYING -INCREASE NUMBER OF BETA CELLS |
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What does glucagon do?
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INCREASE BLOOD GLUCOSE BY STIMULATING GLUCOSE PRODUCTION BY THE LIVER
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2 new incretin based drugs
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EXENATIDE, SITAGLIPTIN
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How does exenatide work?
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PEPTIDE GLP-1 RECEPTOR AGONIST THAT IS NOT DEGRADED BY DPP-4 (LIKE GLP-1 AND GIP)
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How does sitagliptin work?
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RAISES INCRETIN LEVELS BY SPECIFICALLY INHIBITING DPP-4
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What type of input (think NS) to the pancreatic beta cells stimulates insulin secretion?
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PARASYMPATHETIC
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Sensory stimuli and neural inputs that are activated when food is first eaten
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CEPHALIC PHASE
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What cranial nerve is involved in feedforward for insulin secretion?
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VEGUS
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why does sympathetic input to beta cells inhibit insulin secretion during exercise?
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-MUSCLE CELLS USING GLUCOSE FAST (ACTIVATE FUEL-PRODUCING MECHANISMS)
-PREVENT GLUCOSE UPTAKE BY NON-MUSCLE CELLS (WHICH INSULIN STIMULATES) |
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What is the adrenal medulla considered in regards to the NS?
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MODIFIED SYMPATHETIC GANGLION
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What are cells in the adrenal medulla innervated by?
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SYMPATHETIC PREGANGLIONIC NEURONS
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What does the adrenal medulla release?
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EPI AND NOREPI WHICH BIND TO ADRENERGIC RECEPTORS (JUST LIKE SYMPATHETIC STIMULATION)
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3 types of nerual regulation of hormone release
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-AUTONOMIC INNERVATION OF THE PANCREAS
-ADRENAL MEDULLA -NEUROSECRETORY CELLS |
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Main difference between typical neurons and neurosecretory cells
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TERMINALS OF NEUROSECRETORY CELLS ARE ADJACENT TO CAPILLARIES
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Where are neurosecretory cells found?
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HYPOTHALAMUS
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What does the hypothalamus control?
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ANS, FEEDING, DRINKING, STRESS, SLEEP, TEMP, SEX
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2 types of neurosecretory cells
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MAGNOCELLULAR CELLS, PARVOCELLULAR CELLS
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Physical makeup of magnocellular cells
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LARGE W/ LONG AXONS THAT TERMINATE IN THE POSTERIOR PITUITARY (NEUROHYPOPHYSIS)
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Physical makeup of parvocellular cells
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SMALL W/ SHORT AXONS THAT TERMINATE AT A CAPILLARY-RICH BULGE AT THE BASE OF THE HYPOTHALAMUS (MEDIAN EMINENCE)
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What/how do parvocellular cells regulate hormone synthesis?
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HORMONES RELEASED BY PARVOCELLULAR CELLS REGULATE HORMONE SECRETION BY CELLS OF THE ANTERIOR PITUITARY VIA THE HYPOPHYSEAL PORTAL VESSELS
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Where are hormones secreted that have the distinctive feature of regulating their own secretion through negative feedback inhibition?
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HYPOTHALAMUS AND PITUITARY
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In negative feedback inhibition, what do hormones inhibit the secretion of?
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TROPIC HORMONES
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How does cortisol use negative feedback inhibition?
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INHIBITS SECRETION OF CRH AND ACTH. LESS CRH SECRETION LEADS TO LESS ACTH WHICH LEADS TO LESS STIMULATION OF THE ZONA FASCICULATA AND ADRENAL CORTEX TO SECRETE CORTISOL.
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Why is negative feedback inhibition important?
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RESULTS IN HORMONE HOMEOSTASIS
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How does negative feedback inhibition work in an iodine-deficient goiter?
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IODINE LEVELS TOO LOW
-> T3 LEVELS FALL AND NEGATIVE FEEDBACK IS REDUCED -> MORE TRH AND TSH SECRETED (HYPOTHALAMUS AND ANTERIOR PITUITARY) -> TSH STIMULATES PROLIFERATION OF FOLLICLE CELLS -> THYROID GLAND ENLARGES -> MORE CELLS - TRY TO USE ALL IODINE PRESENT TO COMPENSATE AND PREVENT HYPOTHYROIDISM |
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High cortisol
Low ACTH |
TUMOR IN ADRENAL GLAND
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High cortisol
High ACTH |
TUMOR IN THE ANTERIOR PITUITARY
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Low cortisol
High ACTH |
DAMAGE TO THE ADRENAL GLAND
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Low cortisol
Low ACTH |
HYPOPITUITARY ADRENAL INSUFFICIENCY
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Hyper secretion of cortisol (hypercortisolism) - What disease and what does it lead to?
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CUSHING'S SYNDROME
-> INSULIN RESISTANCE, EXCESSIVE BONE RESORPTION, HYPERTENSION, CENTRAL OBESITY |
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A tumor in the pituitary gland is called
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PITUITARY ADENOMA
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When does Cushing's syndrome become Cushing's disease?
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CUSHING SYNDROME CAUSED BY A PITUITARY TUMOR(CORTISOL AND ACTH LEVELS WILL BOTH BE HIGH)
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What is Cushing's SYNDROME caused by?
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ADRENAL TUMOR
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What is hyposecretion of cortisol called?
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ADRENAL INSUFFICIENCY
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Hyposecretion of corisol caused by the adrenal gland is called...
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PRIMARY ADRENAL SUFFICIENCY
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In primary adrenal insufficiency, what will generalized damage to the adrenal cortex cause?
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HYPOSECRETION OF ALDOSTERONE
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What does aldosterone do?
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REGULATES Na+ AND K+ BALANCE IN ECF
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Adrenal insufficiency involving both cortisol and aldosterone hypersecretion is called...
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ADDISON'S DISEASE
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ACTH levels in primary adrenal insufficiency?
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HIGH BECAUSE OF RELEASE OF THE PITUITARY FROM NEGATIVE FEEDBACK INHIBITION
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Secondary adrenal insufficiency is AKA...
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HYPOPITUITARY ADRENAL INSUFFICIENCY
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Disease where abnormally low levels of ACTH lead to a hyposecretion of cortisol?
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HYPOPITUITARY ADRENAL INSUFFICIENCY
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Secondary adrenal insufficiency can occur after a high dose of...
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GLUCOCORTICOID THERAPY (GLUCOCORTICOID RECEPTOR IS THE RECEPTOR FOR CORTISOL)
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Name a hormone that inhibits ACTH secretion
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CORTISOL
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Tropic hormone that stimulates proliferation of thyroid follicle cells
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TSH
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In an iodine-deficient goiter, what hormones should increase?
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TRH, TSH
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Thyroid hormone deficiency in gestation and early post-natal life results in...
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ENDEMIC CRETINISM - DISORDER OF MENTAL RETARDATION AND POOR GROWTH
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Having adequate thryroid hormone levels is called...
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EUTHYROID
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Most commen cause of hyperthyroidism in US
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GRAVES DISEASE
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What happens in Graves Disease?
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-> Antibodies bind and activate the TSH receptor
-> More T3 and T4 produced -> Negative feedback inhibition increases, but thyroid hormone production stays high |
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Symptomes of Graves Disease
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head intolerance, tachycardia, nervousnes, sweating
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Drug used to treat Graves Disease symptoms
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beta adrenergic antagonists
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Surgical removal of the thyroid gland is called...
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thyroidectomy
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Most common cause of hypothyroidism in US
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Hashimoto's Thyroiditis
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Treatments for hypothyroidism
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Thyroxine (T4) therapy
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2 most important hormones for maintaining Ca++ levels
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PTH and 1,25(OH)2D3 (active form of Vit D)
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Major regulator in Ca++ homeostasis
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PTH
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What is PTH secretion stimulated by?
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hypocalcemia
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3 mechanisms PTH works by to maintain Ca++ levels
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1. stimulate release of Ca++ from bone --> BONE RESORPTION
2. decrease urinary loss of Ca++ --> STIMULATE Ca++ REABSORPTION 3. indirectly stimulate synthesis of vit D by kidney --> Ca++ ABSORPTION |
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How does PTH stimulate bone resorbtion?
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Osteoblasts express PTH receptors. PTH stimulation of osteoblasts causes them to express a signaling molecule that activates osteoclasts
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Where does Ca++ reabsorption occur?
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Kidney tubules
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In addition to Ca++ reabsorption, what does PTH do in the kidney tubules?
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Inhibits phosphate reabsorption
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What causes secondary hyperparathyroidism?
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Hypocalcemia stimulates high levels of PTH secretion
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Hyperparathyroidism treatments
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-> Vit D
-> Ca++ supplements -> Cinacalcet |
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How does Cinacalcet work?
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Calcimimetic drug that binds to the Ca++ receptor on cells in the parathyroid gland, inhibiting the secretion of PTH
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Steps in bone resorption
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1. osteoclast tightly adheres to bone
2. membrane adjacent to bone differentiates as the ruffled membrane 3. ruffled membrane acidify the compartment adjacent to the bone 4. acid dissolves minerals in bone and digestive enzymes break down type 1 collagen 5. osteoclast dies by apoptosis |
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Steps of osteoclastogenesis
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-> PTH binds to PTH receptors on osteoblasts
-> osteoblasts express RANK-L -> osteoclast precursors bind with RANK -> |
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Decoy receptor for RANK-L on osteoblasts
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osteoprotegrin
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What ratio determines the extent of bone reabsorption?
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RANK-L : osteoprotegrin
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Partial reduction of bone mass is called...
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osteopenia
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Severe reduction in bone mass is called...
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osteoporosis
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2 hormones that suppress the production of signals that promote osteoclastogenesis
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estrogen and testosterone
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Osteoporosis treatments
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-> hormone replacement therapy
-> bisphosphonates -> SERM -> calcitonin -> teriparatide -> strontium ranelate |
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2 examples of bisphosphonates
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alendronate, risendronate
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How do bisphosphonates work?
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inhibit osteoclast activity and induce osteoclast apoptosis
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How do SERM's work?
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Selective Estrogen Receptor Modulator --> bind to estrogen receptors and act as agonists or antagonists depending on the tissue
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SERM example
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Raloxifene
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How does Calcitonin work?
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Reduces Ca++ in ECF --> binds to receptors on osteoclasts to inhibit bone resorption (works oppositly to PTH -- given as nasal spray or injection)
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How does Teriparatide work?
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Peptide analog of PTH --> intermittent treatment stimulates osteoblasts either by promoting osteoblast survival or stimulating osteoblast proliferation -- only treatment that involves new bone deposition
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Test for T2DM
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oral glucose tolerance test
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An oral glucose tolerance test measures what 2 things?
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1. ability of beta cells to secrete insulin
2. responsiveness of cells in the body to insulin |
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A pre-diabetic stage is called...
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Impaired glucose homeostasis
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2 ways to have impaired glucose homeostasis
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1. impaired fasting glucose
2. impaired glucose tolerance |
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Higher than normal blood insulin levels is called...
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hyperinsulinemia
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4 ways adiposity leads to insulin resistance
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1. access to receptor (lipid deposits in non-adipose tissues)
2. metabolic alterations 3. insulin signal transduction pathway 4. adipocyte changes in regulatory molecules |
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How does adipocyte changes in regulatory molecules lead to insulin resistance?
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Regulatory molecules = adipokines
--> Resistin and TNF-alpha increase (responsible for increasing insulin resistance) --> adiponectin decreases (responsible for increasing insulin sensitivity) --> adipocytes have an enzyme that changes inactive cortisol metabolite back into cortisol |
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4 ways to improve insulin sensitivity
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1. diet
2. exercise 3. metformin 4. thiazolidinediones |
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Hormone that tries to keep weight at set point
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leptin
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How does exercise help diabetes?
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exercise promotes the translocation of glucose transporters to the muscle cell plasma membrane
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How does metformin work?
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--> activates AMP-activated pronated kinase (AMPK) which activates enzymes involved in catabolism and inhibits enzymes involved in anabolism
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How do thiazolidinediones (TZD's) work?
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--> agonist for intracellular receptor PPAR-gamma --> ligands bound to PPAR-gamma --> transcription factor that stimulates adipocyte differentiation and lipogenesis
--> also increase adiponectin which increases insulin sensitivity |
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Visceral adipocytes express an enzyme that produces this active hormone from an inactive metabolite
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cortisol
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What is the goal for treatments of diabetes mellitus?
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glycemic control
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What does chronic hyperglycemia lead to?
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abnormal glycosylation of molecules in tissues
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Major diabetes complications
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- cardiovascular disease
- nephropathy - retinopathy - peripheral neuropathy - foot ulcers |
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In practice, glycemic control is measured by...
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HbA1c or percentage of glycosylated hemoglobin
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2 drug areas that increase insulin secretion
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1. Sulfonylureas and Meglitinides
2. Incretin-based therapies |
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How do sulfonylureas and meglitinides work?
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Bind to and block ATP-sensitive K+ channels on pancreatic beta cells causing depolarization and increased insulin secretion
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What is a potential problem with sulfonylureas?
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They can induce too much insulin secretion and hypoglycemia can result
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Gastrointestinal hormones that increase insulin secretion are called...
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incretins
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2 drugs that are expamles of Incretin-based therapies
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1. Exenatide
2. Sitagliptin |
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How does exenatide work?
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--GLP-1 agonist resistant to digestion by DPP-4
--Decreases glucagon secretion |
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Why does Sitagliptin work longer than exenatide?
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It INHIBITS DPP-4
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2 drugs that decrease glucagon secretion
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1. exenatide
2. pramlintide |
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How does pramlintide work?
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analog of amylin which is produced by pancreatic beta cells and inhibits glucagon secretion in slows stomach emptying
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From where is glucagon secreted?
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alpha cells in the pancreatic islets of Langerhans
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What is glucagon?
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A postabsorptive state hormone that functions to stimulate hepatic glucose production
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2 hormones that delay stomach emptying
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GLP-1 and amylin
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