Endocrine System I_posted.PDF

5/13/20 Objectives Describe the major...

5/13/20 Objectives Describe the major functions of the endocrine system. Define the terms hormone, endocrine gland, endocrine tissue (organ), and target cell. Compare and contrast how the nervous and endocrine systems control body function, with emphasis on the mechanisms by which the controlling signals are transferred through the body and the time course of the response(s) and action(s). Endocrine System I List the major chemical classes of hormones found in the human body. Describe how each class is transported in the blood. Compare and contrast the types of receptors (cell membrane or intracellular) that each class binds to. Compare and contrast the mechanism of response that each class elicits (i.e., change in gene expression or change in an intracellular pathway via phosphorylation mechanism) and relate the response mechanism to the biochemical nature of the hormone molecule. List and describe several types of stimuli that control production and secretion of hormones. Describe the roles of negative and positive feedback in controlling hormone release Define the terms paracrine and autocrine List two major types of eicosanoids and discuss their production and functions. Discuss the production and function of growth factors. Justify whether or not paracrines, autocrines and growth factors should be considered to be part of the endocrine system. 1 2 Characteristic Endocrine System Nervous System Messenger Hormone Neurotransmitter Site of action Distal Proximal The Endocrine System Onset of action Hours to days Milliseconds Duration of action Seconds to days Milliseconds Regulates and controls many metabolic processes Target cells Cells with specified Muscle, Gland or receptor nerve Helps maintain body homeostasis Endocrine – e.g., maintaining blood glucose levels during erratic food intake gland Serves as one of the two major control systems of the body Neuron Regulatory Systems – with the nervous system Hormone Nerve Blood signal Target cells Target cells Neurotransmitter (a) Nervous system (b) Endocrine system 3 4 Endocrine vs. Exocrine Glands The Endocrine System Exocrine glands – Secrete a product into a duct for delivery to target Composed of endocrine glands located throughout the body Ex: pancreas – synthesize and secrete hormones – released into the blood and transported through the body Endocrine glands – Secrete a product into interstitial fluid and ultimately into the Target cells blood stream – cells with a specific receptor for a hormone – bind hormone – Major Endocrine glands Pineal initiates or inhibits selective cell activities Pituitary Thyroid Parathyroid Adrenal Glands 5 6 1  5/13/20 Organs Containing Endocrine Cells Hormones and Glands in General Physiological classes of chemical messengers & Hypothalamus regulators Thymus 1. Intracellular Pancreas cAMP, Ca2+, IP3 (inositol triphosphate) Gonads 2. NT Ach, NE, serotonin Kidneys 3. Neuromodulator Stomach NE, neuropeptides Liver 4. Neurohormones Small intestine ADH, OT Skin 5. Glandular hormones Insulin Heart 6. Local hormones Adipose Prostaglandins, histamine Placenta 7. Pheromones 7 8 Categories of Circulating Hormones A. Steroid Hormones 1. Lipid Soluble Lipid-soluble molecules Steroid hormone A. Steroid Hormones synthesized from cholesterol Lipid-soluble Formed from cholesterol Includes steroids produced in Produced by gonads and adrenal cortex 2. Water Soluble gonads CH 2 OH A. Protein Hormones Includes steroid synthesized by C O adrenal cortex H 3C B. Biogenic Amines (monoamines) HO OH – Aldosterone, cortisol etc. C. Local Hormones Calcitriol (vitamin D) sometimes H 3C classified in this group O Example: Cortisol (a) 9 10 A. Protein Hormones A. Water Soluble-Peptide/Protein Hormones Most hormones are in this category – Hypothalamus & Pituitary Composed of small chain of amino acids Protein hormone HRF, HIF, OT, ADH, hGH, PrL, TSH, ACTH, FSH, LH, Water-soluble Water-soluble MSH Includes polypeptides, between 14 to 199 Consists of amino acid chains Three subgroups – Pancreas amino acids Polypeptides Oligopeptides somatostatin, pancreatic polypeptide – e.g., insulin, glucagon, parathyroid Glycoproteins hormone, hGH – Thyroid – Includes oligopeptides, between 3 to 10 H 2N calcitonin amino acids – Stomach & Small Intestine e.g., oxytocin, antidiuretic hormone Gastrin, secretin, CCK (cholecystokinin), GIP (glucose – Includes glycoproteins dependent insulinotropic peptide) composed of proteins with attached carbohydrate – Kidneys e.g., follicle-stimulating hormone, COOH erthropoietin thyroid-stimulating hormone Example: Parathyroid hormone – Adipose (b) leptin 11 12 2  5/13/20 B. Biogenic Amines Modified amino acids or monoamines Includes: – Catecholamines released from adrenal Biogenic amine medulla Water-soluble (except thyroid hormone) Derived from amino acid that is – Catecholamines modified (e.g., tyrosine) Dopamine, Tyrosine – Histamine H 2N CH 2 Histidine HO CH 2 – Serotonin & Melatonin Tryptophan – Thyroid hormone* released from HO thyroid gland OH Water-soluble except for thyroid hormone Example: Norepinephrine – contains two tyrosine amino acids containing a nonpolar ring 13 14 C. Local Hormones Hormone Transport: Transport in the Blood Large group of signaling molecules Transport of water-soluble hormones – Do not circulate within the blood – Readily dissolve Released from cells that produce them Cytosol – Are easily transported in aqueous environment – Bind with same cell (autocrine) or – E.g., parathyroid hormone neighboring cells (paracrine) Interstitial Plasma membrane Transport of lipid-soluble hormones – sometimes not classified as hormones fluid – Do not readily dissolve Eicosanoids Phospholipid Phospholipase A2 acts on a – Require carrier molecules 1 phospholipid molecule within water-soluble proteins synthesized by the liver – A primary type of local hormone the plasma membrane to “ferry” the hormone molecules within the blood – Derived from phospholipids Phospolipase A2 release a fatty acid molecule called arachidonic acid. – Selectivity – Synthesized through series of enzymes O bind only one lipid-soluble molecule from arachidonic acid C Ex: leukotrienes, prostaglandins, and OH – e.g., thyroxin-binding globulin (TBG) for thromboxanes T3/T4 others nonselective Functions Arachidonic acid 2 Various other enzymes transporting numerous lipid-soluble molecules Different enzymes act on arachidonic acid – Main role in inflammation as part of body’s defenses to produce eicosanoids. – e.g., albumin – Initiate smooth muscle contraction Eicosanoids (e.g., leukotrienes, – Stimulate pain receptors prostaglandins, thromboxanes) 15 16 Hormone Transport: Transport in the Blood Target Cells: Interactions with Hormones Transport of lipid-soluble hormones Hormone targets – Binding between hormone and carrier only – Hormones contacting all tissues of temporary the body may detach and reattach – Only interact with target cells that bound hormone, attached to carrier have specific receptor Unbound (free) hormone, not attached – Interactions between hormones and only unbound hormone able to exit blood and receptors bind to receptors on target organs differences between lipid-soluble – small percentage of hormone in blood and water-soluble hormones 17 18 3  5/13/20 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1 The unbound lipid-soluble hormone diffuses readily through 1 Lipid Soluble Unbound hormone the plasma membrane and binds with an intracellular receptor, either within the cytosol or Hormone the nucleus to form a Bound hormone-receptor complex. hormone Carrier Hormone-receptor 2 The hormone-receptor complex protein Hormone complex then binds with a specific receptor Hormone diffuses from blood to interstitial fluid DNA sequence called a hormone-response element. 3 This binding stimulates mRNA synthesis. Hormone- receptor 4 mRNA exits the nucleus and Through the cell membrane into the cell is translated by a ribosome in Amino acids complex 2 the cytosol. A new protein is synthesized. Blood Ribosome Nuclear mRNA DNA First messenger binds to receptor in cytosol or nucleus if cell is target membrane Hormone- response 3 element mRNA Hormone receptor complex translocates to the nucleus where it binds to the 4 synthesis hormone response element and alters gene expression mRNA Plasma Protein DNAà transcriptionà mRNAàtranslationà protein membrane Interstitial fluid Cytosol Protein changes cell activity 19 20 Lipid-soluble Hormones Water-soluble Hormones Hormone Binding and the Activation of G Protein Relatively small, nonpolar molecules – G protein Able to diffuse across the plasma membrane internal plasma membrane protein complex Bind to intracellular receptors in cytosol or nucleus in inactive state, guanine diphosphate (GDP) bound – form hormone-receptor complex in active state, guanine triphosphate (GTP) bound activated by binding of hormone Hormone-response elements goes on to activate one of two enzymatic cascades regions of DNA where hormone & receptor – adenylate cyclase (AC) complex bind – phospholipase C (PLC) Results in transcription of mRNA Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Translation resulting in protein synthesis Water-soluble hormone 1 Hormone (first messenger) binds to receptor and induces shape change to activate the receptor. GDP: Guanine diphosphate GTP: Guanine triphosphate Receptor May result in alteration in cell structure Interstitial protein Hormone Receptor fluid May result in shift of target cells’ metabolic activity E.g., with increased testosterone synthesis – cellular increase in specific protein synthesis Cytosol 2 G protein binds to G protein Activated G protein – leads to larger muscles, deeper voice, and facial hair Inactive activated receptor. GTP 3 GDP is "bumped off" and GTP binds to GTP 4 Activated G protein (with GTP) is released from the growth GDP G protein G protein; G protein receptor and moves along the inside of the plasma GDP is then activated. membrane, which results in formation or availability of second messenger (see figure 17.9). 21 22 Water-soluble Hormones Water Soluble Hormones 1. Adenylate Cyclase (AC) Activity – Adenylate cyclase, plasma membrane protein increases formation of second messenger, cAMP from ATP Hormone binds to extrinsic protein receptor on target cell membrane protein kinase (PK) activated by cAMP – phosphorylates other molecules – results in activation or inhibition of molecules Hormone receptor complex activates G-Protein cAMP is degraded by phosphodiesterase – E.g., glucagon, antidiuretic hormone, epinephrine G-Protein activates Adenylate cyclase (AC) AC converts ATP- cAMP (second messenger) Adenylate cyclase Interstitial fluid cAMP activates protein kinases (PKs) 1 2 1 Activated G protein binds to and causes activation of the plasma membrane enzyme adenylate PKs activate or inhibit other enzymes Cytosol cAMP cyclase. ATP 2 Adenylate cylase converts ATP molecules to cAMP GTP molecules. Activated G protein 3 3 cAMP serves as the “second messenger” by cAMP is degraded by phosphdiesterase (PDE) Activated activating protein kinase A (a phosphorylating protein kinase enzyme that adds phosphate to other molecules; A enzymes these molecules may be activated or inhibited as a result). (a) Activated G protein “turns on” adenylate cyclase. 23 24 4  5/13/20 Water Soluble Hormones- Water-soluble Hormones Phospholipase C Activity 2. Phospholipase C Activity Hormone binds to extrinsic protein receptor on target cell membrane – Phospholipase C, different plasma membrane protein initiates second type of enzymatic cascade when bound by G protein splits PIP2, phosphoatidylinostitol bisphosphate Hormone receptor complex activates G-Protein results in the formation of two secondary messenger molecules: – diacylglycerol (DAG) and inositol triphosphate (IP3) G-Protein splits PIP2 (phosphatidylinositol biphosphate) A. Action of DAG second messenger remaining in plasma membrane activates protein kinase C enzyme in turn phosphorylates other molecules DAG (2nd messenger) IP3 (2nd messenger) B. Action of IP 3 second messenger diffusing from plasma membrane to cytosol Activates Protein Kinase C Increases intracellular Ca2+ increases intracellular Ca2+ concentration releases Ca2+ in endoplasmic reticulum or Ca2+ channels in membrane acts as a third messenger by: Phosphorylates other Acts as 3rd messenger: binds molecules calmodulin, activates protein – activating protein kinase directly or by binding calmodulin kinases or alters ion flow via – or by altering flow of ions through ion channels channels 25 26 Water-soluble Hormones Phospholipase C Activity Action of Water-Soluble Hormones – Hormones functioning through activation of phospholipase C oxytocin Multiple results possible from hormone activation antidiuretic hormone epinephrine – e.g., activation or inhibition of enzymatic pathways – stimulation of growth through cellular reproduction Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. mitosis Interstitial fluid Phospholipase C Ion channel – stimulation of cellular secretions – changes in membrane permeability PIP2 1 Activated 1 Activated G protein binds to and causes activation of the plasma membrane enzyme phospholipase C. – muscle contraction or relaxation DAG DAG protein Cytosol result dependent on hormone, messenger types, and 3c 2 Phospholipase C splits PIP2 into two second 3a kinase C 2 messengers: DAG (diaclyglycerol) and IP3 (inositol GTP Ca2+ triphosphate). Activated G protein IP3 Calmodulin 3a DAG activates protein kinase C (a phosphorylating enzyme). enzymes phosphorylated 3b IP3 increases Ca2+ in cytosol (by stimulating Ca2+ release from the endoplasmic reticulum [ER] and – Ex: glucagon from pancreatic cells vs oxytocin from posterior 3b Ca2+ 3c entry across the plasma membrane from the interstitial fluid). pituitary Endoplasmic reticulum Activated protein 3c Ca2+ acts as a third messenger to activate protein kinase enzymes kinase enzymes (Ca2+ does this directly or by first binding to calmodulin). Ca2+ may also alter activity (b) Activated G protein “turns on” phopholipase C. of ion channel within the plasma membrane. 27 28 Action of Water-Soluble Hormones Water-soluble Hormones Glucagon (Adenylate cyclase) Oxytocin (Phospholipase C) Intracellular Enzyme Cascade and Amplification of Stimuli: low blood glucose Stimuli: childbirth Response combines with receptors in binds membrane receptors – Signaling pathway advantages: plasma membranes of liver cells of smooth muscle cells in amplifies signal at each enzymatic step causes increase in cAMP uterus – more molecules activated at each step – leads to greater specific response synthesis increases production of IP3 with multistep pathways, more places to fine tune & regulate pathway – 2nd messenger – 2 nd messenger activities causes activation of kinase A enzymes increases intracellular Ca 2+ – Signaling pathway controls leads to phosphorylation of causes stronger uterine need mechanisms to quickly inactivate intermediates specific enzymes muscle contractions to e.g., breaking down second messengers glucose released from liver expel baby e.g., terminating enzyme activities cells 29 30 5  5/13/20 1. Number of Receptors Degree of Cellular Response Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Fluctuations in receptor number 1. Number of receptors Receptor fluctuations Up-regulation Down-regulation – Degree and direction tightly 2. Receptor Interactions regulated – Directly influences degree of cellular response – Up-regulation increase number of receptors Cells up-regulate receptors Cells down-regulate receptors in and hormone sensitivity in response to reduced hormone response to elevated hormone – Down-regulation concentration in the blood. concentration in the blood. decrease number of receptors and hormone sensitivity 31 32 2. Receptor Copyright © The M cG raw-Hill Com panies, Inc. Perm ission required for reproduction or display. Hormone interactions Interactions Target cell receptors Different target cells can house various types of receptors, allowing them Synergistic interactions to bind multiple hormones – Hormones work together to simultaneously. produce a greater effect – e.g., female reproductive structures stronger Adipose cell Liver cell Muscle cell influence by estrogen and progesterone than either alone When multiple hormones Permissive interactions Representative bind to a target cell target cell simultaneously, their – First hormone allows action interactions can produce of second hormone different effects. – Ex: prolactin is required for milk production and oxytocin is required for milk ejection Antagonistic interactions Synergistic Permissive Antagonistic – one hormone opposes the effects of another hormone Hormones work First hormone One hormone together to produce allows action of causes opposite – glucagon increases blood greater effect. second hormone. effect of another. glucose levels – insulin decreasies blood glucose levels (b) 33 6