The document discusses hormone signal transduction pathways. It defines hormones as chemical messengers that target specific cells. There are four major modes of intracellular signal transduction: synaptic, paracrine, autocrine, and endocrine. The endocrine system includes endocrine glands that release hormones directly into the bloodstream. Hormones can be steroid hormones derived from cholesterol or non-steroid hormones like proteins and peptides. Hormones bind to intracellular or cell surface receptors and trigger second messenger pathways that alter cellular activity. Common second messengers include cyclic AMP and cyclic GMP. The document outlines several classes of cell surface receptors like G-protein coupled receptors and enzyme-linked receptors and their roles in signal transduction.

1. Hormone
Signal transduction
pathway
Presented by: Dr. Afrisham
In the name of God 1

2. Outlines
 Introduction
 Major modes of intracellular signal transduction
 Endocrine system
 Types of Hormones
 Types of hormone receptors
 Second messengers
 Major classes of cell surface receptors
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3. Introduction
 The endocrine system includes the endocrine glands and their hormones
 The function of the endocrine system is to secrete hormones into the
bloodstream.
 Hormone: A Chemical messenger which targets a specific group of
cells, in order to cause that group of cells do some activity or stop doing
an activity.
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4. Basic elements of a signal transduction
pathway at the cellular level
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5. Four major modes of intracellular
signal transduction
 Synaptic for neuronal
 Paracrine
 Autocrine
 Endocrine
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6. Four major modes of intracellular
signal transduction
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7. Four major modes of intracellular
signal transduction
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8. Endocrine system
 Exocrine glands release their secretions into ducts, or tubes
 Liver: Bile released into the gallbladder, then through a duct into the small intestine
 Pancreas: releases pancreatic juice into the small intestine via a duct.
 Endocrine Glands are called ductless glands
 Release hormones directly into the bloodstream
 Blood transports hormones throughout the body
 Each hormone acts on only a certain kind of tissue called its target tissue.
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9. Endocrine system
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10. Endocrine system
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11. Hormones control several major processes
 Reproduction
 Growth and development
 Mobilization of body defenses
 Maintenance of much of homeostasis
 Regulation of metabolism
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12. Types of Hormones
 Steroid Hormones
 Derived from cholesterol. They are sex hormones and adrenal cortex hormones Ex.
Estrogen, testosterone. Cortisol.
 Non-steroid Hormones
 Amines, proteins, peptides, glycoproteins, most hormones Ex. OT, FSH, TSH.
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13. Categories and examples of hormones
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14. Types of Hormones
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15. The nature of hormone action
 Cell communication involves three steps.
 For a hormone to have an effect, it must bind to protein receptors on or
inside a target cell.
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16. Types of hormone receptors
 Intracellular receptors
 Receptors at the plasma membrane
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17. Intracellular receptors
 Steroid hormones are made from cholesterol and can diffuse across the
plasma membrane.
 Most steroid hormones form a hormone-receptor complex that binds to a
promoter inside the nucleus and alters the expression of specific genes.
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18. Intracellular receptors
 Steroid hormones
 Non-steroid hormones
 Thyroid hormone
 The active metabolite of vitamin D3
 Retinoic acid
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19. Receptors at the plasma membrane
 Large amine, peptide and protein hormones bind to a receptor at the
plasma membrane.
 Binding triggers formation of a second messenger (molecule that relays
signal into cell).
 Enzyme converts ATP to cAMP.
 cAMP activates a cascading series of reactions.
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20. Receptors at the plasma membrane
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21. Second messengers
 Ions
 Water-soluble second messengers
 Lipid second messengers
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22. Major classes of cell surface receptors
 Ligand-gated ion Channel Receptor
 Enzyme-linked receptors
 Cytokine Receptors
 G-protein-coupled receptors
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23. Major classes of cell surface receptors or
secreted signaling molecules
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24. Major classes of cell surface receptors or
secreted signaling molecules
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25. Enzyme-linked receptors
 Their intracellular domains have catalytic capacities that may
include protein kinase, protein phosphatase, protease, or nucleotide
phosphodiesterase activities.
 They are involved cellular response, such as cell division,
programmed cell death, or cell differentiation.
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26. Enzyme-linked receptors
 The most common catalytic receptors have tyrosine kinase activity.
 These receptor tyrosine kinases (RTK) include the receptors for
epidermal growth factor (EGF), platelet-derived growth factor
(PDGF), insulin, and many other polypeptide growth factors.
 A smaller number of catalytic receptors have serine/threonine
kinase activity.
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27. Clinical points related to enzyme-linked
receptors
 Overexpression of the human EGF receptor characterizes bladder, breast,
kidney, prostate, and lung cancers. It can be detected and treated.
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28. G-protein-coupled receptors
 GPCR binds an extraordinarily diverse range of agonistic ligands
including proteins, peptides, amino acid derivatives, catecholamines,
lipids, nucleotides, and nucleosides.
 These ligands include hormones, neurotransmitters, and local
mediators.
 The GPCR play important roles in endocrine, synaptic, paracrine, or
autocrine signaling in virtually all tissues and cell types.
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29. G-protein-coupled receptors
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30. G-protein-coupled receptors
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31. Regulation Of Cyclic-AMP synthesis and
degradation
 Many metabolic and behavioral responses to different hormones and
neurotransmitters are mediated by increases in intracellular cAMP.
 Cells can actively regulate both the synthesis and degradation of this
second-messenger.
 During maximal hormonal stimulation, the cAMP concentration can
increase 2 to 100-fold, depending on cell type.
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32. Regulation Of Cyclic-AMP Synthesis and
Degradation
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 The activity of these PDEs can be regulated by
both hormones and certain drugs.
 Cellular cAMP can be increased by inhibition of
the PDEs.
 Xanthine derivatives, such as theophylline and
caffeine, inhibit PDEs resulting in increased
cAMP levels in the absence of hormonal
stimulation.

33. Positive and negative regulation of
adenylate cyclase
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34. Role of protein kinase A in the intracellular
signaling cascades regulated by cAMP
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35. Role of protein kinase A in the intracellular
signaling cascades regulated by cAMP
 cAMP profoundly alters cellular metabolism by altering both the
activity and expression of many catabolic enzymes, including enzymes
involved in both lipid and carbohydrate metabolism.
 Metabolic regulation by cAMP often involves the PKA-mediation of
"secondary" kinases or phosphatases, which actually change the
phosphorylation states of the various enzymes.
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36. Activation of protein kinase C
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37. Regulation of Cyclic-GMP Synthesis and
Degradation
 cGMP is an important second messenger in the regulation of muscle and
non-muscle contractility, in visual signal transduction, and in blood
volume homeostasis.
 Cellular levels of cGMP are dynamically regulated by a balance
between synthetic (guanylate cyclases) and degradative (cGMP
phosphodiesterases) enzymes.
 The binding of nitric oxide (NO) induces conformational changes that
greatly increase catalytic activity of the guanylate cyclase.
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38. Regulation of Cyclic-GMP Synthesis and
Degradation
 NO is enzymatically generated by the actions of nitric oxide synthases
(NOS).
 Because NO readily permeates biological membranes, it can be
produced in one type of cell (e.g., a vascular endothelial cell) and
rapidly diffuse into neighboring cell types (e.g., vascular smooth
muscle cells), wherein it activates soluble guanylate cyclase.
 Accumulation of cGMP in smooth muscle triggers rapid and sustained
relaxation of the contractile apparatus.
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39. Step 1 A peptide hormone
molecule, glucagon, diffuses
from blood into interstitial
fluid bathing the plasma
membrane of a liver cell.
Fig. 35-3, p. 601
Stepped Art
Step 1 A steroid hormone
molecule is moved from
blood into interstitial fluid
bathing a target cell.
Step 2 Being
lipid soluble,
the hormone
easily diffuses
across the
cell’s plasma
membrane.
Step 4 The
hormone–
receptor
complex
triggers
transcription
of a specific
gene.
Step 3 The hormone
diffuses through the
cytoplasm and nuclear
envelope. It binds with
its receptor in the
nucleus.
receptor
hormone–
receptor
complex
Step 5 The
resulting mRNA
moves into the
cytoplasm and is
transcribed into a
protein.
gene
product
unoccupied glucagon
receptor at target cell’s
plasma membrane
cyclic
AMP + Pi
ATP
Step 2 Glucagon
binds with a receptor.
Binding activates an
enzyme that catalyzes the
formation of cyclic AMP
from ATP inside the cell.
Step 3 Cyclic AMP
activates another
enzyme in the cell.
Step 4 The enzyme activated by
cyclic AMP activates another
enzyme, which in
turn activates another kind that
catalyzes the break-
down of glycogen to its
glucose monomers.
Step 5 The
enzyme activated
by cyclic AMP
also inhibits
glycogen synthesis
Hormone Actions

40. Clinical points
 Effects of bacterial toxins such as Vibrio cholerae or Bordetella pertussis on G
proteins.
 Vibrio cholerae toxin induces continuous activation of the adenylate cyclase and
cAMP production.
 In the large intestine, results in a sustained PKA-mediated phosphorylation of
chloride channels that normally regulate salt and water transport.
 The hyperactivation of these channels severely disrupts salt and water transport,
resulting in life-threatening diarrhea.
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41. Clinical points
 Gsα G-protein mutations in pituitary gland tumors and endocrine
diseases.
 Nitric Oxide/cGMP signaling axis as therapeutic targets in cardiac and
vascular disorders.
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42. References
• Devlin TM, editor. Textbook of biochemistry with clinical correlations. John
Wiley & Sons; 2010 Jan 19.
• McPherson RA, Pincus MR. Henry's clinical diagnosis and management by
laboratory methods E-book. Elsevier Health Sciences; 2021 Jun 9.
• Burtis CA, Bruns DE. Tietz fundamentals of clinical chemistry and molecular
diagnostics-e-book. Elsevier Health Sciences; 2014 Aug 14.
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