Introduction to Endocrinology Bill Montague
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Transcript of Introduction to Endocrinology Bill Montague
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Introduction to Endocrinology
Bill MontagueMedical & Social Care EducationMSB [email protected]
http://www.le.ac.uk/bs/resources/
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Plan of Sessions
1. Introduction to Endocrinology
2. Thyroid
3. Adrenal and Anterior Pituitary
4. Tutorial – clinical case studies.
5. Endocrine pancreas and the control of energy metabolism.
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Cell communication
Human body composed of functionally specialised cells & tissues.
Normal function depends on these components working together.
Coordination achieved by communication systems:• endocrine• nervous • immune
All communication systems: • use chemical signals (nervous system also uses electrical signals).• work together, not in isolation.
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Components of the endocrine system
Endocrine tissue
Biologically active chemical
Transport in blood
Target cells (receptors & response)
Inactivation of chemical
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Endocrine glands
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Major classes of hormones in man
4 classes identified on structural grounds:
• polypeptide hormones (>20).
• glycoprotein hormones (4).
• amino acid derivatives (3 major hormones).
• steroid hormones (~10).
proteins
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Importance of structure
Structure determines:
• how they are made, stored & secreted.
• how they are transported in the blood.
• how they affect their target tissue(s).
• how they are inactivated.
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Protein hormones - polypeptides
Largest group.
Most consist of a single chain of amino acids.
Vary in size (number of amino acids):• large = 191 - growth hormone.
• medium = 51 - insulin (two chains – covalently linked).
• small = 3 - thyrotropin releasing hormone.
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Protein hormones - glycoproteins
4 hormones:• thyroid stimulating hormone (TSH).• follicle stimulating hormone (FSH).• luteinizing hormone (LH).• human chorionic gonadotropin (hCG).
Consist of 2 polypeptide chains ( & -subunits) with carbohydrate side chains.
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Protein hormones (polypeptide & glycoprotein)
Synthesised as larger precursor molecules (prohormone).• converted to smaller biologically active hormone during storage.
Stored in vesicles prior to secretion.
Hydrophilic :• easily transported in blood.• do not readily cross cell membranes - receptors on surface of target
cells.• require intracellular signals (2nd messengers).
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Amino acid derivatives
Small molecules synthesised from tyrosine.
HO CH2CH(NH2)COOH
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Amino acid derivatives
Adrenaline (catecholamine)
Stored in vesicles in adrenal medulla.
Hydrophilic (weak):• easily transported.
• requires cell surface receptors & intracellular messengers.
HO
HO CH(OH)-CH2-NH(CH3)
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Amino acid derivatives
Thyroid hormones• Tri-iodothyronine (T3)• Tetra-iodothyronine (T4) = thyroxine
HO O CH2-CH(NH2)-COOH
I I
I
I
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Thyroid hormones
Stored extracellularly in thyroid follicles.
Hydrophobic:• require transport proteins.
• cross cell membranes - intracellular receptors.
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Steroid hormones
All synthesised from cholesterol (C27).
Cholesterol stored in steroid producing tissues as cholesterol esters (cholesterol + fatty acid).
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Steroid hormones
Steroid hormones vary:• number of C-atoms (27, 21,19 or 18).• number of double bonds. • presence and type of side-groups.
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Classes of steroid hormones
C-27• Calciferols - 1,25-dihydroxycholecalciferol (vitamin D)
C-21• Corticosteroids – adrenal cortex
– Gluco-corticoids (cortisol)– Mineralo-corticoids (aldosterone)
• Progestins - progesterone (all steroid producing tissues)
C-19• Androgens - testes, ovary, adrenal cortex (testosterone)
C-18 • Oestrogens – ovary (oestradiol)
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Steroid hormones
Not stored:• synthesised on demand from cholesterol esters stored as lipid
droplets.• synthesis involves activation of enzymes in synthetic pathway.
Hydrophobic molecules• require transport proteins.• able to cross cell membranes – receptors are intracellular
(cytoplasmic and/or nuclear).
Control rate of transcription of specific genes.
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Steroid hormone synthesis
Cholesterol ester
Cholesterol
Progesterone 7-dehydrocholesterol
Testosterone Aldosterone Cortisol Calciferols
Oestradiol
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Components of the endocrine system
Endocrine tissue
Biologically active chemical
Transport in blood
Target cells (receptors & response)
Inactivation of chemical
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Hormone concentrations in blood
Hormone concentration normally low (10-10 - 10-8 M) but can increase dramatically depending on:
• rate of secretion.
• extent of binding to carrier proteins.
• rate of inactivation & excretion.
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Control of hormone secretion
Rate of secretion usually controlled by negative feedback:
• change in a parameter regulated by the hormone.
• concentration of hormone itself or another hormone.
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Control of hormone secretion by change in a parameter regulated by the hormone.
insulin
-cell muscle
[blood glucose]
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Control of hormone secretion by change in a parameter regulated by the hormone.
insulin
-cell muscle
[blood glucose]
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Control of hormone secretion by change in a parameter regulated by the hormone.
insulin
-cell muscle
[blood glucose]
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Control of hormone secretion by concentration of hormone itself or another hormone
Cortisol
ACTH
Adrenal
Anterior Pituitary
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Control of hormone secretion by concentration of hormone itself or another hormone
Cortisol
+
ACTH
Adrenal
Anterior Pituitary
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Control of hormone secretion by concentration of hormone itself or another hormone
Cortisol
ACTH
Adrenal
Anterior Pituitary
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Control of hormone secretion by concentration of hormone itself or another hormone
Cortisol
ACTH
Adrenal
Anterior Pituitary
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Hormone transport
Hydrophobic hormones need transport proteins.
Dynamic equilibrium between bound and free forms of hormone:
H(free) + BP H-BP(bound)
Only free form biologically active.
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Hormone action
Hormones act by binding to receptors on/in target cells.
Magnitude of response depends on:• concentration of active hormone at target tissue.
• receptor number (can be varied).
• affinity of receptor for hormone.
• degree of signal amplification (enzymes involved).
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Mechanism of hormone action
Response
P
R
S
2nd messenger nucleus
S
S DNA
R
R
mRNA
Plasma membrane P
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Target tissue responses
Speed of response varies:
• quick (sec-min) - activation of existing enzymes & other functional proteins.
• slow (hr-days) - synthesis of new enzymes & functional proteins.
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Hormone inactivation
Steroid hormones & amino acid derivatives:• Small change in structure - increased water solubility.• Products excreted (bile, urine).
Protein hormones:• Large change in structure – degraded to amino acids.• Products reused or broken down.
Tissues involved:• Target tissues.• Liver (products in bile & blood).• Kidney (products in urine).
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Hormone functions
Control:• Growth, development & reproduction.• Homeostasis - nutrient & electrolyte.• Response to external stimuli (stress, trauma).
Complex control processes:• many processes controlled by several hormones.• many hormones have several effects.
Failure in these control systems can occur producing clinical problems:
Diabetes, Thyroid disease, Cushing’s & Addison’s diseases
Infertility