Medical Genetics LECTURE 2 CHROMOSOME ANOMALIES Reem Sallam, MD, PhD.
By Dr. Reem M. Sallam Clinical Chemistry Unit Pathology Department College of Medicine, KSU.
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Transcript of By Dr. Reem M. Sallam Clinical Chemistry Unit Pathology Department College of Medicine, KSU.
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General Mechanisms of Hormone Actions
By Dr. Reem M. Sallam
Clinical Chemistry UnitPathology Department
College of Medicine, KSU
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OBJECTIVESBy the end of this lecture, students should
be able to:Acquire the knowledge for general
consequence of hormone-receptor interaction
Understand different mechanisms of action of hormones
Recognize the biomedical importance due to disturbance in the normal mechanisms of hormonal action
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Lecture OutlinesBackgroundFactors determining the response of a target cell to a hormone
Hormone-receptor interaction General features of hormone classes
Classification of hormones by mechanism of action
Biomedical importance
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BackgroundMulticellular organisms depend in
their survival on their adaptation to a constantly changing environment
Intercellular communication is necessary for this adaptation to take place
Human body synthesizes many hormones that can act specifically on different cells of the body
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BackgroundMore than one hormone can affect a given cell type
Hormones can exert many different effects in one cell or in different cells
A target is any cell in which the hormone (ligand) binds to its receptor
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1. The rate of synthesis & secretion of the hormones
2. The conversion of inactive forms of the hormone into the fully active form
3. The rate of hormone clearance from plasma (half-life & excretion)
4. The number, relative activity, and state of occupancy of the specific receptors
5. Post-receptor factors
Factors determining the response of a target cell to a hormone
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Gene transcripti
on
Group II hormones
Stimulus
Group I hormones
Hormone-receptor complex
Transporters,
channels
Protein translocati
on
Protein Modification
Coordinated response to stimulus
Second messengers
Recognition
Hormone release
Signal generation
Effects
Hormone/receptor bindingat the target cells
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General Features of Hormone ClassesGroup II Group I
PolypeptidesGlycoproteinsCatecholamines
SteroidsThyroid Hormones: (T3 & T4)Calcitriol, retinoids
Types
Hydrophilic Lipophilic SolubilityNo Yes Transport
proteinsShort (minutes) Long (hours –
days)Plasma half-life
Plasma membrane Intracellular ReceptorcAMP, cGMP, Ca2+, metabolites of complex phosphoinositols, tyrosine kinase cascades
Receptor-hormone complex
Mediator
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Classification of Hormones by Mechanism of Action
I. Hormones that bind to intracellular receptors (Steroid-Thyroid superfamily):
Steroid hormonesThyroid Hormones (T3 & T4)Calcitriol (active form of vitamin D, 1,25[OH]2-D3)Retinoic acid
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Classification of Hormones by Mechanism of Action continued…
II. Hormones that bind to cell surface receptorsA. The second messenger is cAMP
• Catecholamines (α2- Adrenergic)• Catecholamines (- Adrenergic)• Ant. Pituitary: ACTH, FSH, LH & TSH• ADH (Renal V2-receptor)• Calcitonin & PTH• Glucagon
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Classification of Hormones by Mechanism of Action continued…
II. Hormones that bind to cell surface receptorsB. The second messenger is cGMP
Atrial natriuretic peptide (ANP)Nitric oxide
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Classification of Hormones by Mechanism of Action continued…
II. Hormones that bind to cell surface receptorsC. The second messenger is calcium
or phosphatidylinositol (or both)
• Acetylcholine (muscarinic)• Catecholamines (α1- Adrenergic)• Angiotensin II• ADH (vasopressin): Extra-renal V1-receptor
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Classification of Hormones by Mechanism of Action continued…
II. Hormones that bind to cell surface receptors
D. The second messenger is a tyrosine kinase cascade
Growth Hormone (GH) & ProlactinInsulinErythropoietin
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Group I. Hormones that bind to intracellular receptors
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Mechanism of Action of Steroid-Thyroid Hormones
Steroid Hormones:GlucocorticoidsMineralocorticoidsSex hormones:
Male sex hormones: AndrogensFemale sex hormones: Estrogens
& ProgestinsThyroid Hormones (T3 & T4)
Calcitriol (1,25[OH]2-D3)
Retinoic acid
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Group II. Hormones that bind to cell surface receptorsA. The second messenger is cAMP
• Glucagon• Catecholamines (- Adrenergic)• ADH (Renal V2-receptor)
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Cascade for formation of cAMP by cell-surfacehormones
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Actions of cAMP1 AMP
1Phosphodiesterase
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Х
1. Release of hormone from its receptor(unbound receptor)
2. Dephosphorylation of protein substrate by phosphatase
3. Degradation of cAMP into AMP by phosphodiesterase
4. Inactivation of protein kinase A by a decrease of cAMP
5. Hydrolysis of GTP into GDP
6. Binding of α-subunit to βγ-subunits
7. Inactivation of adenylyl cyclase
Abortion of Hormonal Stimulus
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The activated enzyme is guanylate cyclaseFor Example:
ANP and NO
Group II. Hormones that bind to cell surface receptors
B. The second messenger is cGMP
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Atrial Natriuretic Peptide (ANP)
GC: Gunaylate cyclase
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Group II. Hormones that bind to cell surface receptors
C. The second messenger is calcium or phosphatidylinositol (or both)
• Catecholamines (α1-Adrenergic)
• ADH (vasopressin): Extra-renal V1-receptor
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Calcium/Phosphatidylinositol System
Phospholipase C
Diacylglycerol (DAG)
Inositol Trisphosphate(IP3)
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II. Hormones that bind to cell surface receptorsD. The second messenger is a tyrosine kinase cascade
• Growth hormone and prolactin• Insulin• Erythropoietin
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Mechanism of Insulin action
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Biologic Effects of Insulin
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Biomedical ImportanceExcessive (e.g., hyperthyroidism,
Cushing), deficient (e.g., hypothyroidism, Addison), or inappropriate secretion (e.g., syndrome of inappropriate secretion of ADH “SIADH”) of hormones are major causes of diseases
Pharmacological treatment of these diseases depends on replacement of deficient hormone (hypo-) or use of drugs that interfere with the mechanism of action of the hormones (hyper- or inappropriate)
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THANK YOU