ENDOCRINE.
DR.HAROON RASHID.
OBJECTIVES.
• Define hormone & list the general functions of
hormones in the body.
• Classify hormones according to their chemical
nature.
• Outline the endocrine glands & exemplify
some of their hormones.
• Describe briefly the major mechanisms for
hormone actions.
• Hormone is a chemical substance secreted by ductless
gland into the blood.
• Endocrine glands•
Hypothalamus,
•
Pituitary gland
•
Thyroid Gland.
•
Parathyroid.
•
Heart,Pancrease,
•
•
•
•
•
•
Adernal gland.
Testis
Ovaries etc.
Hypothalamus and posterior
pituitary
Midsagital view
illustrates that
magnocellular neurons
paraventricular and
supraoptic nuclei secrete
oxytocin and
vasopressin directly into
capillaries in the
posterior lobe
We now know
What is the classical
that nearly every
endocrine system?tissue secretes
chemical signals
that act as
hormones, heart,
immune cells,
stomach,
intestines, bone
cells, liver, skin,
glial cells, etc.
www.cushings-help.com/ images/endocrine.jpg
Hormone
A
c
r
o
n
y
m
Hypop
hysial
Cell
Type
Hypothalamic Regulator(s)
Hormonal Function(s)
Corticotropin,
Adrenocorticotr
opin
A
C
T
H
Cortico
trope
+Corticotropin Releasing Hormone, Corticoliberin
(CRH); + Interleukin 1 ; - Glucocortical Steroids (via
CRH); + Vasopressin; + PACAP
Stimulates glucocorticoid production by adrenal
fasiculata & reticularis
T
S
H
Thyrotr
ope
-Thyroxine (T4); +Thyroid Releasing Hormone,
Thyroliberin (TRH); -Somatostatin (SS)
Stimulates thyroxine production by thyroid
Prolactin,
Mammotropin,
Luteotropin
P
R
L
Lactotr
ope;
Mamm
otrope
-Dopamine; + TRH; - SS; + Estrogens; + Oxytocin
Stimulates milk synthesis by secretory epithelium of
breast; supports corpus luteum function
Somatotropin,
Growth
Hormone
G
H
Somat
otrope
+ Growth Hormone Releasing Hormone,
Somatoliberin (GHRH); - SS; + PACAP
Stimulates somatic growth, supports intermediary
metabolism
Follitropin,
Follicle
Stimulating
Hormone
F
S
H
Gonad
otrope
+ Gonadotropin Releasing Hormone, Luteinizing
Hormone Releasing Hormone, Gonadoliberin (GnRH,
LHRH); - Inhibin; - Sex steroids (via LHRH)
Supports growth of ovarian follicles & estradiol
production; Supports Sertoli cell function &
spermatogenesis
Lutropin,
Luteinizing
Hormone
L
H
Gonad
otrope
+ GnRH (LHRH); - Sex steroids (via LHRH in & ); +
Estradiol in near midcycle
Supports late follicular development, ovulation, &
corpus luteum function (especially progesterone
synthesis); Supports testosterone synthesis, Leydig
cell
Melanotropin,
Melanocyte
Stimulating
Hormone
M Melan
S otrope
H
+ CRH
Supports dispersal & synthesis of pigment in
melanocytes; may alter adrenal response to ACTH
Thyrotropin,
Thyroid
Stimulating
Hormone
What are the regulatory products of the
hypothalamus?
What are endocrine systems for?
Endocrine Functions
• Maintain Internal Homeostasis
•
Support Cell Growth
• Coordinate Development
• Coordinate Reproduction
• Facilitate Responses to External Stimuli
ENDOCRINOLOGY
• Two systems control all physiologic processes:
• The nervous system exerts point-to-point control
through nerves, similar to sending messages by
conventional telephone. Nervous control is electrical
in nature and fast.
• The endocrine system broadcasts its hormonal
messages to essentially all cells by secretion into
blood and extracellular fluid. Like a radio broadcast,
it requires a receiver to get the message - in the case
of endocrine messages, cells must bear a receptor for
the hormone being broadcast in order to respond.
Endocrinology
Hormones:
Classification:
I.-Based on distance of target cells:
1.Pracrine 2.Autocrine3.Intracrine
II.Based on chemical nature:
1.Peptides 2. Steroids 3.Derivatives of AA
Biosythesis
1.Peptide hormones:
Gene-mRNA-AA linkage- Polypeptide chains (
preprohormone)- removal of signal peptideformation of prohormone-to-Golgi apparatus
– stored as secretory granules and are
released by exocytosis( ca+ mediates ?)
2. Steroids:Cholesterol to hormone and released
( note: NOT STORED)
1.Peptide hormones:
ER,
Golgi,
secretory
vesicles
Many hydrophobic (lipophilic) hormones are steroids,
derived from cholesterol
Storage
• Steroids: not stored.
• Peptides: to some extent
• Thyroids: reserve of upto 3 months.
• DEGRADATION:
• Usually by Liver & excreted by kidneys.
• Some are inactivated by kidneys.
Transport in blood
1. Protein-peptides & catacholamines:water
soluble & are transported in blood.
2. Steroids & Thyroid hr: insoluble in water, but
when combine with proteins- become water
soluble and are transported. A small portion
of hydrophobic hormones remain free( un
bound with proteins ) and this fraction is
metabolically active. The bound form acts as
reservoir.
Control of hormone secretion
( = Secretion can be stimulated or inhibited)
•
•
•
•
•
•
Other hormones(of Hypothalamus or Ant.pituitary )
Feed back mechanisms- + feedback&-ve
Stress
Biological rhythm
Neural and mental activity
Plasma concentrations of ions or nutrients, as well as binding
globulins
• Environmental changes, e.g., of light or temperature
• One special group of hormones is the tropic hormones that
stimulate the hormone production of other endocrine glands.
For example, thyroid-stimulating hormone (TSH) causes
growth and increased activity of another endocrine gland, the
thyroid, which increases output of thyroid hormones.
• Others.
Regulation
• Positive feedback mechanism-Release of
oxytocin during Lactation-Contraction of
myoepitheial cells-Release of Milk.
• Negative feedback mechanism-Decrease in
concentration of hormone will stimulate the
target gland-Release of hormone occurs.
• Eg-Thyroid,Insulin etc.
NEGATIVE FEEDBACK
Mechanism of action: mainly by
RECEPTORS
•
1.
2.
3.
4.
5.
6.
7.
8.
Receptors:
Only target cells have receptors.
Only fraction of total population of receptors in target cells is
enough for max.effects( Insulin 10% )
Receptors combine with ligands and initiate series of actions(
Ligand=chemical molecule which combine with receptor, it can
be hormone, neurotransmitter,drug)
There is upregulation & down regulation.
A cell may have many different types of receptors for different
sub/hormones( eg. Oxyntic cells have receptors for Ach,
histamine, prostaglandins)
Receptors are degraded and are replaced.
Location: MEMBRANE BOUND OR CYTOSOLIC/NUCLEAR
RECEPTOS : may be linked to- ionic channels of
membrane,Gproteins, enzymes in the cells,may stimulate
transcripting mechanism.
Types of receptors
G-protein coupled receptors
Adenylate cyclase, cAMP and PKA
Types of receptors-
Mechanism of Action of hormones
• For many hormones, including most protein hormones, the
receptor is membrane associated and embedded in the
plasma membrane at the surface of the cell. The interaction
of hormone and receptor typically triggers a cascade of
secondary effects within the cytoplasm of the cell, often
involving phosphorylation or dephosphorylation of various
other cytoplasmic proteins, changes in ion channel
permeability, or increased concentrations of intracellular
molecules that may act as secondary messengers (e.g. cyclic
AMP). Some protein hormones also interact with intracellular
receptors located in the cytoplasm or nucleus by an intracrine
mechanism.
Mechanism of Action of hormones
• For many hormones, including most protein hormones, the
receptor is membrane associated and embedded in the
plasma membrane at the surface of the cell. The interaction
of hormone and receptor typically triggers a cascade of
secondary effects within the cytoplasm of the cell, often
involving phosphorylation or dephosphorylation of various
other cytoplasmic proteins, changes in ion channel
permeability, or increased concentrations of intracellular
molecules that may act as secondary messengers (e.g. cyclic
AMP). Some protein hormones also interact with intracellular
receptors located in the cytoplasm or nucleus by an intracrine
mechanism.
Cell surface receptor action
Second messenger systems
 The generation of second messengers and activation
of specific protein kinases results in changes in the
activity of the target cell which characterizes the
response that the hormone evokes.
 Changes evoked by the actions of second messengers
are usually rapid
Second messenger systems
 Each of these second messenger systems activates a
specific protein kinase enzyme.
These include cyclic nucleotide-dependent protein
kinases
Calcium/calmodulin-dependent protein kinase,
and protein kinase C which depends on diacyl
glycerol binding for activation.
Protein kinase C activity is further increased by
calcium which is released by the action of
inositol phosphates.
Second messengers for cell-surface
receptors
 Second messenger systems include:
 Adenylate cyclase which catalyzes the conversion of ATP to
cyclic AMP;
 Guanylate cyclase which catalyzes the conversion of GMP
to cyclic GMP (cyclic AMP and cyclic GMP are known
collectively as cyclic nucleotides);
 Calcium and calmodulin; phospholipase C which catalyzes
phosphoinositide turnover producing inositol phosphates
and diacyl glycerol.
Mechanism of Action of hormones
• For hormones such as steroid or thyroid hormones, their
receptors are located intracellularly within the cytoplasm of
their target cell. In order to bind their receptors these
hormones must cross the cell membrane. The combined
hormone-receptor complex then moves across the nuclear
membrane into the nucleus of the cell, where it binds to
specific DNA sequences, effectively amplifying or suppressing
the action of certain genes, and affecting protein synthesis.[2]
However, it has been shown that not all steroid receptors are
located intracellularly, some are plasma membrane
associated.[3]
Mechanism of lipid
soluble hormone
action
Effects of hormone
•
•
•
•
•
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Hormone effects vary widely, but can include:
stimulation or inhibition of growth,
In puberty hormones can affect mood and mind
induction or suppression of apoptosis (programmed cell death)
activation or inhibition of the immune system
regulating metabolism
preparation for a new activity (e.g., fighting, fleeing, mating)
preparation for a new phase of life (e.g., puberty, caring for offspring,
menopause)
• controlling the reproductive cycle
• In many cases, one hormone may regulate the production and release of
other hormones
• Many of the responses to hormone signals can be described as serving to
regulate metabolic activity of an organ or tissue.
Estimation of hormones
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•
•
•
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Calorimetric
Bioassay
RIA
ELISA
Chemiluminescence method.