1-Introduction to Endcrine, diabetes .ppt

endokrin

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

4. The Endocrine System

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

7. A Structural Classification of Hormones

8. Correlation of Plasma Half-Life & Metabolic Clearance of Hormones with
Degree of Protein Binding
Hormone Protein
binding (%)
Plasma half-lifeMetabolic 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 PIP
2 into
diacylglycerol (DAG) and IP
3 (both act as second
messengers)
•DAG activates protein kinases; IP
3 triggers
release of Ca
2+
stores
•Ca
2+
(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 (V
2
receptor)
HCG
MSH
CRH
Calcitonin
PTH
Glucagon
GnRH
TRH
PTH
Angiotensin II
ADH (V
1
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. P
L
A
S
M
A

G
H

(

G
/
L
)
CLOCK TIME
P
L
A
S
M
A

C
O
R
T
I
S
O
L

(
n
m
o
l
/
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

30. Feedback Mechanisms
Endocrine
cell
Target
cell
_
+
Biological effects
Endocrine
cell
Target
cell
+
+
Biological effects
Negative Feedback Positive Feedback

31. Negative feedback

32. Measurement of Hormone Concentrations
•Radioimmunoassay (RIA)
•Enzyme-Linked Immunosorbentm Assay
(ELISA)