The Endocrine Physiology
Introduction to Endocrinology
Dr. Khalid Alregaiey
Endocrine System: Overview
• Endcocrinology: It is study of homeostatic
functions of substances called HORMONES, that
are released from glands called endocrine glands
distributed throughout the body.
• Hormones: Are secretions of ductless glands
that are directly released into the blood stream.
They can act on cells in the vicinity or on distant
target cells.
• Endocrine system – the body’s second great
controlling system which influences metabolic
activities of cells by means of hormones
Endocrine System: Overview
• Endocrine glands – pituitary, thyroid,
parathyroid, adrenal, pineal, and thymus
• The pancreas and gonads produce both
hormones and exocrine products
• The hypothalamus has both neural functions
and releases hormones
• Other tissues and organs that produce
hormones – adipose cells, pockets of cells in
the walls of the small intestine, stomach,
kidneys, and heart
The Endocrine System
Autocrines and Paracrines
• Autocrines – chemicals that exert their effects on
the same cells that secrete them
• Paracrines – locally acting chemicals that affect
cells other than those that secrete them
• These are not considered hormones since
hormones are long-distance chemical signals
Types of Hormones
• Amino acid based – most hormones belong to
this class, including:
• Amines (Tyrosine: Caecholamines and Thyroid
hormones, Tryptophan: Melatonin)
• Polypeptide hormones
• protein hormones
• Steroids – Derived from Cholesterol, gonadal
and adrenocortical hormones
• Fatty acid derived: Eicosanoids, derived from
arachidonic leukotrienes and prostaglandins
A Structural Classification of Hormones
Correlation of Plasma Half-Life & Metabolic Clearance of Hormones with
Degree of Protein Binding
Hormone Protein
binding (%)
Plasma half-life Metabolic clearance
(ml/minute)
)
Thyroid
Thyroxine
Triiodothyronine
Steroids
Cortisol
Testosterone
Aldosterone
Proteins
Thyrotropin
Insulin
Antidiuretic hormone
99.97
99.7
94
89
15
little
little
little
6 days
1 day
100 min
85 min
25 min
50 min
8 min
8 min
0.7
18
140
860
1100
50
800
600
MCR = (mg/minute removed)/(mg/ml of plasma) = ml cleared/minute
Circulating Transport Proteins
Specific
Corticosteroid binding globulin
(CBG, transcortin)
Thyroxine binding globulin (TBG)
Sex hormone-binding globulin
(SHBG)
Nonspecific
Albumin
Transthyretin (prealbumin)
Principle Hormone
Transported
Cortisol, aldosterone
Thyroxine, triiodothyronine
Testosterone, estrogen
Most steroids, thyroxine,
triiodothyronine
Thyroxine, some steroids
Transport Protein
Determinants of Free Hormone Receptor Binding
Carrier-bound
hormone
Endocrine
cell
Free
Hormone
Hormone
receptor
Hormone
degradation
Biological
effects
Hormone Action
• Hormones alter target cell activity by one of
the following mechanisms:
• Ion Channel–Linked Receptors.
• G Protein–Linked Hormone Receptors.
• Enzyme-Linked Hormone Receptors.
• Intracellular Hormone Receptors and
Activation of Genes (steroid and thyroid
hormones)
• Hormones circulate to all tissues but only activate
cells referred to as target cells
• Target cells must have specific receptors to
which the hormone binds
Hormone Action
Location of receptors:
• 1. In or on the surface of the cell membrane. The
membrane receptors are specific mostly for the
protein, peptide, and catecholamine hormones.
• 2. In the cell cytoplasm. The primary receptors
for the different steroid hormones are found
mainly in the cytoplasm.
• 3. In the cell nucleus. The receptors for the
thyroid hormones are found in the nucleus and
are believed to be located in direct association
with one or more of the chromosomes.
• Hormone (first messenger) binds to its receptor,
which then binds to a G protein
• The G protein is then activated as it binds GTP,
displacing GDP
• Activated G protein activates the effector enzyme
adenylate cyclase
• Adenylate cyclase generates cAMP (second
messenger) from ATP
• cAMP activates protein kinases, which then cause
cellular effects
Cyclic Adenosine Monophosphate (cAMP)
Second Messenger Mechanism
Cyclic Adenosine Monophosphate (cAMP)
Second Messenger Mechanism
• Hormone binds to the receptor and activates
G protein
• G protein binds and activates a phospholipase
enzyme
• Phospholipase splits the phospholipid PIP2 into
diacylglycerol (DAG) and IP3 (both act as second
messengers)
• DAG activates protein kinases; IP3 triggers
release of Ca2+
stores
• Ca2+
(third messenger) alters cellular responses
Cell Membrane Phospholipid: Second Messenger
System
Cell Membrane Phospholipid: Second Messenger
System
Cytokine Receptors & Tyrosine Kinase Receptors
The Insulin Receptor & Mechanisms of Insulin Action
Protein Hormones - Mechanisms of Action
Adenylyl Cyclase
Mechanism
Guanylate Cyclase
Mechanism
Tyrosine
Kinase/Cytokine
Receptor
Mechanism
Phospholipid
Mechanism
ACTH
LH
FSH
TSH
GHRH
Somatostatin
ADH (V2 receptor)
HCG
MSH
CRH
Calcitonin
PTH
Glucagon
GnRH
TRH
PTH
Angiotensin II
ADH (V1 receptor)
Oxytocin
ANP Insulin
IGF-1
GH
Prolactin
• Steroid hormones and thyroid hormone diffuse easily
into their target cells
• Once inside, they bind and activate a specific
intracellular receptor
• The hormone-receptor complex travels to the nucleus
and binds a DNA-associated receptor protein
• This interaction prompts DNA transcription to produce
mRNA
• The mRNA is translated into proteins, which bring
about a cellular effect
Steroid and Thyroid Hormones
Steroid & Thyroid Hormones - Mechanism of Action
• Target cell activation depends on three factors
• Blood levels of the hormone
• Relative number of receptors on the target cell
• The affinity of those receptors for the hormone
• Up-regulation – target cells form more receptors
in response to the hormone
• Down-regulation – target cells lose receptors in
response to the hormone
Target Cell Activation
• Hormones circulate in the blood in two forms –
free or bound
• Steroids and thyroid hormone are attached to
plasma proteins
Hormone Concentrations in the Blood
• Concentrations of circulating hormone reflect:
• Rate of release
• Speed of inactivation and removal from the
body
• Hormones are removed from the blood by:
• Degrading enzymes
• The kidneys
• Liver enzyme systems
Hormone Concentrations in the Blood
• Three types of hormone interaction
• Permissiveness – one hormone cannot exert its
effects without another hormone being present
• Synergism – the total effect of two hormones
together is greater than the sum of their
individual effects
• Antagonism – one or more hormones opposes
the action of another hormone
Interaction of Hormones at Target Cells
PLASMA
GH
(

G/L)
CLOCK TIME
PLASMA
CORTISOL
(nmol/L)
Hormonal Rhythms
0
4
8
12
8 12 16 20 0 4 8
0
100
200
300
400
500
8 12 16 20 0 4 8
• Blood levels of hormones:
• Are controlled by negative and positive
feedback systems
• Vary only within a narrow desirable range
• Hormones are synthesized and released in
response to humoral, neural, and hormonal
stimuli
Control of Hormone Release
• Negative feedback is most common: for example,
LH from pituitary stimulates the testis to produce
testosterone which in turn feeds back and inhibits
LH secretion
• Positive feedback is less common: examples include
LH stimulation of estrogen which stimulates LH
surge at ovulation
Feedback Control
Feedback Mechanisms
Endocrine
cell
Target
cell
_
+
Biological effects
Endocrine
cell
Target
cell
+
+
Biological effects
Negative Feedback Positive Feedback
Negative feedback
Measurement of Hormone Concentrations
• Radioimmunoassay (RIA)
• Enzyme-Linked Immunosorbentm Assay
(ELISA)

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1-Introduction to Endcrine, diabetes .ppt

  • 1. The Endocrine Physiology Introduction to Endocrinology Dr. Khalid Alregaiey
  • 2. Endocrine System: Overview • Endcocrinology: It is study of homeostatic functions of substances called HORMONES, that are released from glands called endocrine glands distributed throughout the body. • Hormones: Are secretions of ductless glands that are directly released into the blood stream. They can act on cells in the vicinity or on distant target cells. • Endocrine system – the body’s second great controlling system which influences metabolic activities of cells by means of hormones
  • 3. Endocrine System: Overview • Endocrine glands – pituitary, thyroid, parathyroid, adrenal, pineal, and thymus • The pancreas and gonads produce both hormones and exocrine products • The hypothalamus has both neural functions and releases hormones • Other tissues and organs that produce hormones – adipose cells, pockets of cells in the walls of the small intestine, stomach, kidneys, and heart
  • 5. Autocrines and Paracrines • Autocrines – chemicals that exert their effects on the same cells that secrete them • Paracrines – locally acting chemicals that affect cells other than those that secrete them • These are not considered hormones since hormones are long-distance chemical signals
  • 6. Types of Hormones • Amino acid based – most hormones belong to this class, including: • Amines (Tyrosine: Caecholamines and Thyroid hormones, Tryptophan: Melatonin) • Polypeptide hormones • protein hormones • Steroids – Derived from Cholesterol, gonadal and adrenocortical hormones • Fatty acid derived: Eicosanoids, derived from arachidonic leukotrienes and prostaglandins
  • 8. Correlation of Plasma Half-Life & Metabolic Clearance of Hormones with Degree of Protein Binding Hormone Protein binding (%) Plasma half-life Metabolic clearance (ml/minute) ) Thyroid Thyroxine Triiodothyronine Steroids Cortisol Testosterone Aldosterone Proteins Thyrotropin Insulin Antidiuretic hormone 99.97 99.7 94 89 15 little little little 6 days 1 day 100 min 85 min 25 min 50 min 8 min 8 min 0.7 18 140 860 1100 50 800 600 MCR = (mg/minute removed)/(mg/ml of plasma) = ml cleared/minute
  • 9. Circulating Transport Proteins Specific Corticosteroid binding globulin (CBG, transcortin) Thyroxine binding globulin (TBG) Sex hormone-binding globulin (SHBG) Nonspecific Albumin Transthyretin (prealbumin) Principle Hormone Transported Cortisol, aldosterone Thyroxine, triiodothyronine Testosterone, estrogen Most steroids, thyroxine, triiodothyronine Thyroxine, some steroids Transport Protein
  • 10. Determinants of Free Hormone Receptor Binding Carrier-bound hormone Endocrine cell Free Hormone Hormone receptor Hormone degradation Biological effects
  • 11. Hormone Action • Hormones alter target cell activity by one of the following mechanisms: • Ion Channel–Linked Receptors. • G Protein–Linked Hormone Receptors. • Enzyme-Linked Hormone Receptors. • Intracellular Hormone Receptors and Activation of Genes (steroid and thyroid hormones)
  • 12. • Hormones circulate to all tissues but only activate cells referred to as target cells • Target cells must have specific receptors to which the hormone binds Hormone Action
  • 13. Location of receptors: • 1. In or on the surface of the cell membrane. The membrane receptors are specific mostly for the protein, peptide, and catecholamine hormones. • 2. In the cell cytoplasm. The primary receptors for the different steroid hormones are found mainly in the cytoplasm. • 3. In the cell nucleus. The receptors for the thyroid hormones are found in the nucleus and are believed to be located in direct association with one or more of the chromosomes.
  • 14. • Hormone (first messenger) binds to its receptor, which then binds to a G protein • The G protein is then activated as it binds GTP, displacing GDP • Activated G protein activates the effector enzyme adenylate cyclase • Adenylate cyclase generates cAMP (second messenger) from ATP • cAMP activates protein kinases, which then cause cellular effects Cyclic Adenosine Monophosphate (cAMP) Second Messenger Mechanism
  • 15. Cyclic Adenosine Monophosphate (cAMP) Second Messenger Mechanism
  • 16. • Hormone binds to the receptor and activates G protein • G protein binds and activates a phospholipase enzyme • Phospholipase splits the phospholipid PIP2 into diacylglycerol (DAG) and IP3 (both act as second messengers) • DAG activates protein kinases; IP3 triggers release of Ca2+ stores • Ca2+ (third messenger) alters cellular responses Cell Membrane Phospholipid: Second Messenger System
  • 17. Cell Membrane Phospholipid: Second Messenger System
  • 18. Cytokine Receptors & Tyrosine Kinase Receptors
  • 19. The Insulin Receptor & Mechanisms of Insulin Action
  • 20. Protein Hormones - Mechanisms of Action Adenylyl Cyclase Mechanism Guanylate Cyclase Mechanism Tyrosine Kinase/Cytokine Receptor Mechanism Phospholipid Mechanism ACTH LH FSH TSH GHRH Somatostatin ADH (V2 receptor) HCG MSH CRH Calcitonin PTH Glucagon GnRH TRH PTH Angiotensin II ADH (V1 receptor) Oxytocin ANP Insulin IGF-1 GH Prolactin
  • 21. • Steroid hormones and thyroid hormone diffuse easily into their target cells • Once inside, they bind and activate a specific intracellular receptor • The hormone-receptor complex travels to the nucleus and binds a DNA-associated receptor protein • This interaction prompts DNA transcription to produce mRNA • The mRNA is translated into proteins, which bring about a cellular effect Steroid and Thyroid Hormones
  • 22. Steroid & Thyroid Hormones - Mechanism of Action
  • 23. • Target cell activation depends on three factors • Blood levels of the hormone • Relative number of receptors on the target cell • The affinity of those receptors for the hormone • Up-regulation – target cells form more receptors in response to the hormone • Down-regulation – target cells lose receptors in response to the hormone Target Cell Activation
  • 24. • Hormones circulate in the blood in two forms – free or bound • Steroids and thyroid hormone are attached to plasma proteins Hormone Concentrations in the Blood
  • 25. • Concentrations of circulating hormone reflect: • Rate of release • Speed of inactivation and removal from the body • Hormones are removed from the blood by: • Degrading enzymes • The kidneys • Liver enzyme systems Hormone Concentrations in the Blood
  • 26. • Three types of hormone interaction • Permissiveness – one hormone cannot exert its effects without another hormone being present • Synergism – the total effect of two hormones together is greater than the sum of their individual effects • Antagonism – one or more hormones opposes the action of another hormone Interaction of Hormones at Target Cells
  • 27. PLASMA GH (  G/L) CLOCK TIME PLASMA CORTISOL (nmol/L) Hormonal Rhythms 0 4 8 12 8 12 16 20 0 4 8 0 100 200 300 400 500 8 12 16 20 0 4 8
  • 28. • Blood levels of hormones: • Are controlled by negative and positive feedback systems • Vary only within a narrow desirable range • Hormones are synthesized and released in response to humoral, neural, and hormonal stimuli Control of Hormone Release
  • 29. • Negative feedback is most common: for example, LH from pituitary stimulates the testis to produce testosterone which in turn feeds back and inhibits LH secretion • Positive feedback is less common: examples include LH stimulation of estrogen which stimulates LH surge at ovulation Feedback Control
  • 32. Measurement of Hormone Concentrations • Radioimmunoassay (RIA) • Enzyme-Linked Immunosorbentm Assay (ELISA)