Chapter 18. An Introduction to the Endocrine System. Hormone Chemistry

Transcription

1 Chapter 18 An Introduction to the Endocrine System Hormone Chemistry

2 Endocrine System Components endocrine system - glands, tissues, and cells that secrete hormones Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Endocrine cells Target cells endocrine glands organs that are traditional sources of hormones (b) Endocrine system Hormone in bloodstream hormones chemical messengers that are transported by the bloodstream and stimulate physiological responses in cells of another tissue or organ, often a considerable distance away endocrinology the study of this system and the diagnosis and treatment of its disorders Key Steps: 1. Hormone synthesized by tissue. 2. Hormone released into blood. 3. Hormone circulates within cardiovascular system 4. Hormone leaves blood, diffuse to target tissue s receptor. 5. Hormone binds to receptor. 6. Hormone changes metabolism of target tissue.

3 Some Organs Hard to Classify Pancreas (mixed gland) Exocrine digestive enzymes Endocrine insulin / glucagon Hepatocytes (liver cells) defy rigid classification releases hormones releases bile into ducts releases albumin and blood-clotting factors into blood (not hormones)

4 Comparison of Nervous and Endocrine Systems both serve internal communication nervous - both electrical and chemical endocrine - only chemical speed and persistence of response nervous - reacts quickly (1-10 msec), stops quickly endocrine - reacts slowly (hormone release in seconds or days), effect may continue for weeks adaptation to long-term stimuli nervous - response declines (adapts quickly) endocrine - response persists (adapts slowly) area of effect nervous - targeted and specific (one organ) endocrine - general, widespread effects (many organs)

5 Comparison of Nervous and Endocrine Systems several chemicals function as both hormones and neurotransmitters // norepinephrine, cholecystokinin, thyrotropinreleasing hormone, dopamine and antidiuretic hormone some hormones secreted by neuroendocrine cells (neurons) that release their secretion into the bloodstream // oxytocin and catecholamines both systems with overlapping effects on same target cells // norepinephrine and glucagon cause glycogen hydrolysis in liver systems regulate each other // neurons trigger hormone secretion // hormones stimulate or inhibit neurons

6 Communication by the Nervous and Endocrine Systems Neurotransmitter Nerve impulse (a) Nervous system Neuron Target cells Endocrine cells Target cells (b) Endocrine system Hormone in bloodstream

7 Major Endocrine Organs Pineal gland Hypothalamus Pituitary gland Thyroid gland Thymus Adrenal gland Pancreas Parathyroid glands Posterior view Trachea Gonads: Ovary (female) Testis (male) organs of endocrine system / know these

8

9

10 Hormone chemistry. What are the different chemical properties of hormones and what are their mechanisms of actions?

11 Three Chemical Classes steroids derived from cholesterol secreted by gonads and adrenal glands estrogens, progesterone, testosterone, cortisol, corticosterone, aldosterone, DHEA, and calcitriol peptides (and glycoproteins) created from chains of amino acids secreted by pituitary and hypothalamus oxytocin, antidiuretic hormone, releasing and inhibiting hormones, and anterior pituitary hormones O HO (a) Steroids (c) Peptides Hormone Chemistry Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Angiotensin II Testosterone Estradiol Insulin OH OH HO HO H 2 N (b) Monoamines I I H C CH 2 O OH Thyroxine OH COOH CH CH 2 Epinephrine Pro Thr Tyr Phe Asn Cys Tyr Asn Glu Leu Lys Phe S Gln Thr Gly Tyr Gly Arg Leu lle Glu S Ser Val Gly Cys Glu Cys Gln Val lle Cys Ser Thr Cys Leu Tyr Arg Val Tyr Leu Asp lle Ala His Glu Val Pro Phe Leu His Ser Gly Cys Leu His Gln Asn Val Phe S S S S I I NH CH 2

12 Three Chemical Classes Hormone Chemistry Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. monoamines (biogenic amines) OH H 2 N H C COOH CH 2 derived from amino acids secreted by adrenal, pineal, and thyroid glands epinephrine, norepinephrine, melatonin, and thyroid hormone O HO Testosterone Estradiol OH HO HO I I O I I OH Thyroxine OH CH CH 2 Epinephrine NH CH 2 (a) Steroids (b) Monoamines Note: all hormones are made from either cholesterol or amino acids (with carbohydrate added to make glycoproteins). Pro Thr Tyr Phe Asn Cys Tyr Asn Glu Leu Lys Phe S Gln Thr Gly Tyr Gly Arg Leu lle Glu S Ser Val Gly Cys Glu Cys Gln Val lle Cys Ser Thr Cys Leu Tyr Arg Val Tyr Leu Asp lle Ala His Glu Val Pro Phe Leu His Ser Gly Cys Leu His Gln Angiotensin II Insulin S S S S (c) Peptides Asn Val Phe

13 Hormone Synthesis: Steroid Hormones Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. HO Cholesterol C O O Progesterone CH 2 OH OH C O HO OH HO CH O 2 OH C O HC O Testosterone O Cortisol (hydrocortisone) O Aldosterone OH HO Estradiol synthesized from cholesterol differs in functional groups attached to 4-ringed steroid backbone

14 Peptides synthesized using same metabolic pathways as any other proteinprotein first formed as an inactive pre-prohormone several amino acids in peptide function as a signal that guides it into cisterna of rough endoplasmic reticulum signal peptide removed to form prohormone Golgi does final transformation to hormone packaged for secretion

15 Hormone Synthesis: Insulin begins as pre-proinsulin, then becomes proinsulin Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. when connecting peptide is removed, two polypeptide chains are formed that make up insulin C peptide Proinsulin Insulin

16 Monoamines These are synthesized from amino acid E.g. /// Melatonin (the hormone released by the pineal gland) is synthesized from the amino acid tryptophan /// transformed into the brain neutrotransmitter seratonin which is then transformed into melatonin E.g. /// thyroid hormone is composed of 2 tyrosines (tyrosine is an amino acid)

17 Thyroid Hormone Synthesis (not on exam) Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Thyroid follicle Blood capillary Transport proteins I Iodide 1 Iodide absorption and oxidation 5 1 Follicle cell 2 Thyroglobulin synthesis and secretion T 3 T 4 3 Iodine added to tyrosines of thyroglobulin 4 Thyroglobulin uptake and hydrolysis Lysosome 4 I 2 Thyroglobulin 5 Release of T 4 and a small amount of T 3 into the blood I * Iodine Stored thyroglobulin 3

18 T 3 and T 4 Synthesis (not on exam) Follicular cells absorb iodide (I - ) ions from blood and store in lumen as a reactive form of iodine synthesize thyroglobulin and store in lumen // forms colloid // contains lots of tyrosine tyrosine and iodine combine to form thyroxine (T 4 ) bound to thyroglobulin stored in follicle

19 T 3 and T 4 Synthesis (not on exam) TSH stimulates follicular cells to remove T 4 from thyroglobulin for release into plasma most T 3 is produced in liver or by target cells removing an iodine from circulating T 4 95% T 4 and 5% T 3

20 Hormone Transport most monoamines and peptides are hydrophilic // mix easily with blood plasma steroids and thyroid hormone are hydrophobic Hydrophobic hormones need to bind to transport proteins (albumins and globulins which are synthesized by the liver) bound hormones have longer half-life protected from liver enzymes and kidney filtration transport proteins protect circulating hormones being broken down by enzymes in the plasma and liver being filtered out of the blood by the kidneys only hydrophobic hormones that become unbound are able to leaves capillaries to reach target cell

21 Hormone Transport thyroid hormone /// exception to the rule /// protein based hormone but binds to three transport proteins in the plasma albumin, thyretin and TGB (thyroxine-binding globulin) more than 99% of circulating TH is protein bound Some steroid hormones bind to globulins // transcortin is the transport protein for cortisol Aldosterone // short half-life 85% unbound 15% binds weakly to albumin and others

22 Hormone Receptors hormones stimulate only those cells that have receptors for them receptors are protein or glycoprotein molecules: // on plasma membrane, in the cytoplasm, or in the nucleus receptors act like switches turning on metabolic pathways when hormone binds to them usually each target cell has a few thousand receptors for a given hormone receptor-hormone interactions exhibit specificity and saturation specific receptor for each hormone saturated when all receptor molecules are occupied by hormone molecules

23 Hormone Mode of Action Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. hydrophobic hormones Transport protein Hydrophilic hormone Receptor in plasma membrane Target cell penetrate plasma membrane and enter nucleus Free hormones Secondmessenger activation act directly on the genes changing target cell physiology Bound hormone Blood Hydrophobic hormone Receptor in Tissue fluid nucleus estrogen, progesterone, thyroid hormone act on nuclear receptors take several hours to days to show effect due to lag for protein synthesis

24 Hormone Mode of Action Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. hydrophilic hormones Transport protein Hydrophilic hormone Receptor in plasma membrane Target cell cannot penetrate into target cell Free hormones Secondmessenger activation must stimulate physiology indirectly Second messenger systems Bound hormone Blood Hydrophobic hormone Receptor in Tissue fluid nucleus

25 Thyroid Hormone TBG thyroid hormone enters target cell by diffusion mostly as T 4 with little metabolic effect T 3 T 4 Various metabolic effects within target cell, T 4 is converted to more potent T 3 Protein synthesis mrna DNA T 3 enters target cells and binds to receptors in chromatin T 4 T 3 I activates genes make a muscle protein (myosin) enhancing cardiac muscle response to sympathetic stimulation Blood Tissue fluid Target cell strengthening heartbeat

26 Peptides and Catecholamines: Hydrophilic Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. hormone binds to cell-surface receptor Hormone 1 Receptor G protein Adenylate cyclase 1 Hormone receptor binding activates a G protein. 2 G protein activates adenylate cyclase. receptor linked to second messenger system on other side of the membrane 2 G G GTP GDP + P i ATP camp + PP 3 i 4 3 Adenylate cyclase produces camp. 4 camp activates protein kinases. activates G protein which Inactive protein kinase Activated protein kinase ACTH FSH LH PTH TSH Glucagon Calcitonin Catecholamines Inactive enzymes 5 Activated enzymes Protein kinases phosphorylate enzymes. This activates some enzymes and deactivates others. Activated enzymes catalyze metabolic reactions with a wide range of possible effects on the cell. activates adenylate cyclase Enzyme substrates Enzyme products Various metabolic effects produces camp activates or inhibits enzymes

27 Other Second Messengers Diacylglycerol (DAG) pathway Inositol triphosphate (IP 3 ) pathway 1 Hormone Ca 2+ -gated ion channel Ca 2+ IP 3 -gated Ca 2+ channei Hormone 1 Receptor Phospholipase Phospholipase Receptor 3 DAG G 2 IP G 3 G 4 6 Inactive Activated 8 5 PK PK 2 IP 3 G Various metabolic effects Enzyme Activated PK 9 10 Calmodulin Ca 2+ 7 IP 3 Hormones ADH TRH OT LHRH Catecholamines Key DAG G IP 3 PK Diacylglycerol G protein Inositol triphosphate Protein kinase Inactive PK Smooth ER diacylglycerol (diglyceride) second-messenger system inositol triphosphate second-messenger system act on cell metabolism in a variety of ways

28 Enzyme Amplification Small stimulus hormones are extraordinarily potent chemicals Hormone camp and protein kinase Activated enzymes Metabolic product Great effect Reaction cascade (time) one hormone molecule can trigger the synthesis of many enzyme molecules. very small stimulus can produce very large effect circulating concentrations very low

29 Modulation of Target Cell Sensitivity Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Hormone Receptor target cell sensitivity adjusted by changing the number of receptors Low receptor density Weak response (a ) Up-regulation Increased receptor density Increased sensitivity Response Stronger response up-regulation means number of receptors is increased // sensitivity is increased down-regulation reduces number of receptors High receptor density Strong response (b ) Down-regulation Reduced receptor density Reduced sensitivity Response Diminished response cell less sensitive to hormone happens with long-term exposure to high hormone concentrations bind to other receptors converted to different hormone

30 Hormone Interactions most cells sensitive to more than one hormone and exhibit interactive effects synergistic effects multiple hormones act together for greater effect // synergism between FSH and testosterone on sperm production permissive effects one hormone enhances the target organ s response to a second later hormone // estrogen prepares uterus for action of progesterone antagonistic effects one hormone opposes the action of another // insulin lowers blood glucose and glycogen raises it

31 Hormone Clearance hormone signals must be turned off when they have served their purpose most hormones are taken up and degraded by liver and kidney // excreted in bile or urine metabolic clearance rate (MCR) rate of hormone removal from the blood half-life - time required to clear 50% of hormone from the blood faster the MCF, the shorter is the half-life