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HORMONE: 
MECHANISM & ACTION 
By 
DR KHALED SALEH ALGARIRI 
NOVEMBER 2014
WHAT ARE HORMONES? 
• Natural organic substances, that regulate growth, 
metabolism and other functions of an organism 
• They are simply biochemical messengers 
• They can be classified according to the chemical 
composition, organs where they work e.g 
reproductive hormones in the reproductive 
organs, and if they either act on the same cell 
producing them i.e. autocrine or paracrine
GENERAL PRINCIPLES OF HORMONE 
ACTION 
• Trophic hormone:- A hormone that has its primary function the regulation 
of hormone secretion by another endocrine gland 
• Synergism-when different hormones work together and have a greater 
effect than individual hormone action 
• Permissiveness-a small amount of one hormone allows a second hormone 
to have its full effect on a target cell; i.e. first hormone ‘permits’ the full 
action of the second hormone 
• Antagonism-one hormone produces the opposite effect of the other 
• The processes involve in both negative and positive feedback. For example, 
if A>B>C>D, increase in D causes inhibition of A i.e. negative feedback. If D 
decreases, A production is triggered, i.e. positive feedback.
Mechanism & action hormone
GENERAL CHARACTERISTICS 
OF HORMONES 
 Not secreted at a uniform rate 
 Exert their effects in biocatalytic amounts 
 Turnover is varied and usually rapid 
 Exert multiple actions 
 Exhibit high degree of specificity 
 Different tissues may respond differently to a 
given hormone
MECHANISM OF HORMONE ACTION 
The hormones fall into two general classes based on 
their solubility in water. 
 1. Hydrophilic Hormone: The water soluble hormone. 
They are transported simply dissolved in blood 
 Examples: the catecholamines (epinephrine and 
norepinephrine) and peptide/protein hormones. 
 2. Lipophilic Hormone: They are poorly soluble in water. 
So they cannot be dissolved in watery blood. They bind to 
plasma protein and present in the blood in protein bound 
form. They are lipid soluble. 
 Examples: The lipid soluble hormones include thyroid 
hormone, steroid hormones and Vitamin D3
Broad Classification (Structure) 
Hydrophillic Lipophillic 
Proteins, peptide hormones 
& catecholamines 
Steroid and thyroid hormones 
Primarily act through second 
messenger system 
Activate genes on binding with 
receptors in the nucleus 
Circulate mainly dissolved in 
the plasma 
Largely bound to plasma proteins
Signal Amplification Via 2nd Messenger Pathways 
Initial signal is in the form of hormone which acts 
as ligand whose concentration is just one/per 
receptor. The hormonal response has got multiple 
steps, and each step multiplies the signal 
(cascading effect) that finally leading to million 
fold amplification, i.e. one hormone molecule 
mediating its effect through million of molecules. 
This process is known as signal amplification.
Mechanism & action hormone
MODE OF HORMONE ACTION 
• Generally hormones work in two ways 
 1-synthesis of new protein molecules 
 2- changing cell permeability 
• Lipid-soluble hormones involves in ‘ 
whereas water-soluble 
hormones involves in ‘
TYPES OF RECEPTOR 
RECEPTOR 
INTERNAL 
NUCLEAR 
CYTOPLASMIC 
EXTERNAL 
CELL 
MEMBRANE
MEMBRANE RECEPTOR 
 Receptors present in or on the surface of the 
cell membrane. 
Types 
 Ion channel-linked receptor 
 G –protein couple receptor 
 Enzyme –linked receptor 
 E.g., Proteins, peptides, & catecholamines
CYTOPLASMIC RECEPTOR 
 Receptors present in cell cytoplasm 
 E.g., Steroid hormones.
NUCLEAR RECEPTOR 
 Receptors present in nucleus & 
there is direct association with one 
or more chromosomes. 
 E.g., Thyroid hormones, Retinoid 
hormones, Vitamin-D.
Mechanism & action hormone
LIPID-SOLUBLE HORMONES
HOW LIPID-SOLUBLE HORMONES 
WORK? 
• Binding to specific cell receptor in the cell membrane 
and form hormone-cell receptor complex, which 
diffuses to nucleus 
• The receptor is eventually released for re-use 
• Steroid activates a specific gene to produce mRNA 
• mRNA pass out into the cytoplasm and initiates 
protein [enzyme] synthesis 
why do they penetrate the cell? 
 the whole process is called mobile-receptor 
hypothesis in which a steroid hormone is not attached 
to the plasma membrane, but seem to move freely in 
the nucleoplasm
HOW LIPID-SOLUBLE HORMONES 
WORK? 
 Step1: Free lipophilic hormone (hormone not bound with its 
plasma protein carrier) diffuses through the plasma membrane 
of the target cell and binds with the receptor which is 
intracellularly located inside the cytosol/or in the nucleus. 
 Step2. Each receptor has specific binding region with hormone 
and another region with binding with DNA. Receptor alone 
cannot bind to DNA unless it binds to hormone. Once the 
hormone is bound to receptor, the hormone receptor complex 
binds to specific region of DNA known as Hormone response 
element(HRE). 
 Step3: Transcription of gene 
 Step4: m RNA transported out of nucleus into the cytoplasm 
 Step5: Translation at Ribosome 
 Step6: Protein/enzyme released from ribosome 
 Step7: protein/enzyme mediate ultimate response
STEROID HORMONES: MOLECULAR 
ACTION
Lipophilic hormone response mediated through Cytosolic receptor/nuclear 
receptor
HOW LIPID-SOLUBLE HORMONES 
WORK?
WATER-SOLUBLE HORMONES
HOW WATER-SOLUBLE HORMONES 
WORK?
HOW WATER-SOLUBLE HORMONES 
WORK? 
• ●1 A water-soluble hormone (the first messenger) diffuses from the 
blood through interstitial fluid and then binds to its receptor at the 
exterior surface of a target cell’s plasma membrane. The hormone– 
receptor complex activates a membrane protein called a G protein. The 
activated G protein in turn activates adenylate cyclase. 
• ●2 Adenylate cyclase converts ATP into cyclic AMP (cAMP). Because the 
enzyme’s active site is on the inner surface of the plasma membrane, this 
reaction occurs in the cytosol of the cell. 
• ●3 Cyclic AMP (the second messenger) activates one or more protein 
kinases, which may be free in the cytosol or bound to the plasma 
membrane. A protein kinase is an enzyme that phosphorylates (adds a 
phosphate group to) other cellular proteins (such as enzymes). The donor 
of the phosphate group is ATP, which is converted to ADP.
HOW WATER-SOLUBLE HORMONES 
WORK? 
• ●4 Activated protein kinases phosphorylate one or more cellular proteins. 
Phosphorylation activates some of these proteins and inactivates others, 
rather like turning a switch on or off. 
• ●5 Phosphorylated proteins in turn cause reactions that produce 
physiological responses. Different protein kinases exist within different 
target cells and within different organelles of the same target cell. Thus, 
one protein kinase might trigger glycogen synthesis, a second might cause 
the breakdown of triglyceride, a third may promote protein synthesis, and 
so forth. As noted in step ●4 phosphorylation by a protein kinase can also 
inhibit certain proteins. For example, some of the kinases unleashed when 
epinephrine binds to liver cells inactivate an enzyme needed for glycogen 
synthesis 
. 
• ●6 After a brief period, an enzyme called phosphodiesterase inactivates 
cAMP. Thus, the cell’s response is turned off unless new hormone 
molecules continue to bind to their receptors in the plasma membrane
HOW WATER-SOLUBLE HORMONES 
WORK? 
• The whole process above is called 
also called 
. In this 
instance, the first messenger delivers 
message to fixed receptors in the target cell’s 
plasma membrane. The message then is 
passed to the cell where second messenger 
triggers appropriate cellular changes
REGULATION OF HORMONE SECRETION
FEEDBACK CONTROL
- ve feedback control 
+ ve feedback 
control
Mechanism & action hormone

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Mechanism & action hormone

  • 1. HORMONE: MECHANISM & ACTION By DR KHALED SALEH ALGARIRI NOVEMBER 2014
  • 2. WHAT ARE HORMONES? • Natural organic substances, that regulate growth, metabolism and other functions of an organism • They are simply biochemical messengers • They can be classified according to the chemical composition, organs where they work e.g reproductive hormones in the reproductive organs, and if they either act on the same cell producing them i.e. autocrine or paracrine
  • 3. GENERAL PRINCIPLES OF HORMONE ACTION • Trophic hormone:- A hormone that has its primary function the regulation of hormone secretion by another endocrine gland • Synergism-when different hormones work together and have a greater effect than individual hormone action • Permissiveness-a small amount of one hormone allows a second hormone to have its full effect on a target cell; i.e. first hormone ‘permits’ the full action of the second hormone • Antagonism-one hormone produces the opposite effect of the other • The processes involve in both negative and positive feedback. For example, if A>B>C>D, increase in D causes inhibition of A i.e. negative feedback. If D decreases, A production is triggered, i.e. positive feedback.
  • 5. GENERAL CHARACTERISTICS OF HORMONES  Not secreted at a uniform rate  Exert their effects in biocatalytic amounts  Turnover is varied and usually rapid  Exert multiple actions  Exhibit high degree of specificity  Different tissues may respond differently to a given hormone
  • 6. MECHANISM OF HORMONE ACTION The hormones fall into two general classes based on their solubility in water.  1. Hydrophilic Hormone: The water soluble hormone. They are transported simply dissolved in blood  Examples: the catecholamines (epinephrine and norepinephrine) and peptide/protein hormones.  2. Lipophilic Hormone: They are poorly soluble in water. So they cannot be dissolved in watery blood. They bind to plasma protein and present in the blood in protein bound form. They are lipid soluble.  Examples: The lipid soluble hormones include thyroid hormone, steroid hormones and Vitamin D3
  • 7. Broad Classification (Structure) Hydrophillic Lipophillic Proteins, peptide hormones & catecholamines Steroid and thyroid hormones Primarily act through second messenger system Activate genes on binding with receptors in the nucleus Circulate mainly dissolved in the plasma Largely bound to plasma proteins
  • 8. Signal Amplification Via 2nd Messenger Pathways Initial signal is in the form of hormone which acts as ligand whose concentration is just one/per receptor. The hormonal response has got multiple steps, and each step multiplies the signal (cascading effect) that finally leading to million fold amplification, i.e. one hormone molecule mediating its effect through million of molecules. This process is known as signal amplification.
  • 10. MODE OF HORMONE ACTION • Generally hormones work in two ways  1-synthesis of new protein molecules  2- changing cell permeability • Lipid-soluble hormones involves in ‘ whereas water-soluble hormones involves in ‘
  • 11. TYPES OF RECEPTOR RECEPTOR INTERNAL NUCLEAR CYTOPLASMIC EXTERNAL CELL MEMBRANE
  • 12. MEMBRANE RECEPTOR  Receptors present in or on the surface of the cell membrane. Types  Ion channel-linked receptor  G –protein couple receptor  Enzyme –linked receptor  E.g., Proteins, peptides, & catecholamines
  • 13. CYTOPLASMIC RECEPTOR  Receptors present in cell cytoplasm  E.g., Steroid hormones.
  • 14. NUCLEAR RECEPTOR  Receptors present in nucleus & there is direct association with one or more chromosomes.  E.g., Thyroid hormones, Retinoid hormones, Vitamin-D.
  • 17. HOW LIPID-SOLUBLE HORMONES WORK? • Binding to specific cell receptor in the cell membrane and form hormone-cell receptor complex, which diffuses to nucleus • The receptor is eventually released for re-use • Steroid activates a specific gene to produce mRNA • mRNA pass out into the cytoplasm and initiates protein [enzyme] synthesis why do they penetrate the cell?  the whole process is called mobile-receptor hypothesis in which a steroid hormone is not attached to the plasma membrane, but seem to move freely in the nucleoplasm
  • 18. HOW LIPID-SOLUBLE HORMONES WORK?  Step1: Free lipophilic hormone (hormone not bound with its plasma protein carrier) diffuses through the plasma membrane of the target cell and binds with the receptor which is intracellularly located inside the cytosol/or in the nucleus.  Step2. Each receptor has specific binding region with hormone and another region with binding with DNA. Receptor alone cannot bind to DNA unless it binds to hormone. Once the hormone is bound to receptor, the hormone receptor complex binds to specific region of DNA known as Hormone response element(HRE).  Step3: Transcription of gene  Step4: m RNA transported out of nucleus into the cytoplasm  Step5: Translation at Ribosome  Step6: Protein/enzyme released from ribosome  Step7: protein/enzyme mediate ultimate response
  • 20. Lipophilic hormone response mediated through Cytosolic receptor/nuclear receptor
  • 24. HOW WATER-SOLUBLE HORMONES WORK? • ●1 A water-soluble hormone (the first messenger) diffuses from the blood through interstitial fluid and then binds to its receptor at the exterior surface of a target cell’s plasma membrane. The hormone– receptor complex activates a membrane protein called a G protein. The activated G protein in turn activates adenylate cyclase. • ●2 Adenylate cyclase converts ATP into cyclic AMP (cAMP). Because the enzyme’s active site is on the inner surface of the plasma membrane, this reaction occurs in the cytosol of the cell. • ●3 Cyclic AMP (the second messenger) activates one or more protein kinases, which may be free in the cytosol or bound to the plasma membrane. A protein kinase is an enzyme that phosphorylates (adds a phosphate group to) other cellular proteins (such as enzymes). The donor of the phosphate group is ATP, which is converted to ADP.
  • 25. HOW WATER-SOLUBLE HORMONES WORK? • ●4 Activated protein kinases phosphorylate one or more cellular proteins. Phosphorylation activates some of these proteins and inactivates others, rather like turning a switch on or off. • ●5 Phosphorylated proteins in turn cause reactions that produce physiological responses. Different protein kinases exist within different target cells and within different organelles of the same target cell. Thus, one protein kinase might trigger glycogen synthesis, a second might cause the breakdown of triglyceride, a third may promote protein synthesis, and so forth. As noted in step ●4 phosphorylation by a protein kinase can also inhibit certain proteins. For example, some of the kinases unleashed when epinephrine binds to liver cells inactivate an enzyme needed for glycogen synthesis . • ●6 After a brief period, an enzyme called phosphodiesterase inactivates cAMP. Thus, the cell’s response is turned off unless new hormone molecules continue to bind to their receptors in the plasma membrane
  • 26. HOW WATER-SOLUBLE HORMONES WORK? • The whole process above is called also called . In this instance, the first messenger delivers message to fixed receptors in the target cell’s plasma membrane. The message then is passed to the cell where second messenger triggers appropriate cellular changes
  • 29. - ve feedback control + ve feedback control