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Introduction to Endocrinology
Bill MontagueMedical & Social Care EducationMSB [email protected]
http://www.le.ac.uk/bs/resources/
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.
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.
Components of the endocrine system
Endocrine tissue
Biologically active chemical
Transport in blood
Target cells (receptors & response)
Inactivation of chemical
Endocrine glands
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
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.
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.
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.
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).
Amino acid derivatives
Small molecules synthesised from tyrosine.
HO CH2CH(NH2)COOH
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)
Amino acid derivatives
Thyroid hormones• Tri-iodothyronine (T3)• Tetra-iodothyronine (T4) = thyroxine
HO O CH2-CH(NH2)-COOH
I I
I
I
Thyroid hormones
Stored extracellularly in thyroid follicles.
Hydrophobic:• require transport proteins.
• cross cell membranes - intracellular receptors.
Steroid hormones
All synthesised from cholesterol (C27).
Cholesterol stored in steroid producing tissues as cholesterol esters (cholesterol + fatty acid).
Steroid hormones
Steroid hormones vary:• number of C-atoms (27, 21,19 or 18).• number of double bonds. • presence and type of side-groups.
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)
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.
Steroid hormone synthesis
Cholesterol ester
Cholesterol
Progesterone 7-dehydrocholesterol
Testosterone Aldosterone Cortisol Calciferols
Oestradiol
Components of the endocrine system
Endocrine tissue
Biologically active chemical
Transport in blood
Target cells (receptors & response)
Inactivation of chemical
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.
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.
Control of hormone secretion by change in a parameter regulated by the hormone.
insulin
-cell muscle
[blood glucose]
Control of hormone secretion by change in a parameter regulated by the hormone.
insulin
-cell muscle
[blood glucose]
Control of hormone secretion by change in a parameter regulated by the hormone.
insulin
-cell muscle
[blood glucose]
Control of hormone secretion by concentration of hormone itself or another hormone
Cortisol
ACTH
Adrenal
Anterior Pituitary
Control of hormone secretion by concentration of hormone itself or another hormone
Cortisol
+
ACTH
Adrenal
Anterior Pituitary
Control of hormone secretion by concentration of hormone itself or another hormone
Cortisol
ACTH
Adrenal
Anterior Pituitary
Control of hormone secretion by concentration of hormone itself or another hormone
Cortisol
ACTH
Adrenal
Anterior Pituitary
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.
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).
Mechanism of hormone action
Response
P
R
S
2nd messenger nucleus
S
S DNA
R
R
mRNA
Plasma membrane P
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.
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).
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