Introduction

ENDOCRINE SYSTEM

Branch of biologic science that is concerned

with the actions of hormones and the organs in
which the hormone are formed
Its boundaries included study of the anatomy
and physiological function of the major
endocrine organs, the secretory products of
these organs, the mechanisms of hormone
action, and the clinical manifestations of
hormone dysfunction

Endocrine Organs
Adipocytes
Leptin
Adiponectin
Interleukin
etc.

GI Tract
Ghrelin
CCK
GIP
GLP-1,2
etc.
Heart
Natriuretic peptide

Kidney
Renin
Erythropoietin

Hormones:
Endocrine, Paracrine, Autocrine, Juxtacrine,
Intracrine action

Endocrine System and Nerve System = 2 main

control systems of body
Endocrine organs located throughout body
Actions mediate all tissues
Control of Endocrine System through feedback
mechanisms

Endocrine cell
Autocrine
signalling
Cell
Body

Receptor

Blood
stream

Extracellular
fluid

Paracrine
signalling

Axon
Nerve
Terminal

Target
cell

Synapse

Activation of intracellular
messenger pathways

Fig. Signaling by (A) hormones, (B) local mediators, (C) neurotransmitters

CLASSIFICATION OF HORMONES
Based on location of receptors: 2 groups
Tabel. General features of hormone group

Feature

Group I

Group II

Type

Steroid
Iodothyronine
Calcitriol

Polypeptides
Proteins
Glycoproteins
Cathecolamines

Solubility

Lipophylic

Hydrophylic

Transfort proteins

Yes

No

Plasma half-life

Long (hours, days)

Short (minutes)

Receptor

Intracellular

Plasma membrane

Mediators

Receptor-hormon
complex

cAMP, cGMP, Ca2+,, DAG,

kinase cascades,
phophatidyl inositide,
others

Chemical composition of
hormones
Precursor

Type
compound

Example of
hormone

Protein
Protein
Clevage of
Peptide
peptide
Thyroxine
Clevage of a. acid

GH
ACTH
Thyroxine

Cholesetrol

Steroid

Cortisol
1,25 OHD3

Amino acid

Modified a. acid Epinephrine

Tripeptide
TRH

Fatty acid

Retinoid
Eicosanoid

Retinoic acid
Prostaglandin E1

Hormone action
DEFINITION
Ligand
Receptor
Effector
First-second messenger

LIGAND
Any small molecules that binds
specifically to a receptor site
Agonist - antagonist
Ex.: hormone, drugs, etc.

RECEPTOR
A molecule that recognizes
specifically a ligand or family of
ligands, and which in response
to ligand binding brings about
regulation of a cellular process

EFFECTOR
Transmembrane molecules/ enzyme or
ion channel
Adenylate cyclase, Ca2+ channel,
Phospholipase C

SECOND MESSENGER
Be maintained at low concentration in the resting
cell
Be produced only in response to activation of
spesific receptors
Be produced in proportion to the size of
extracellular signal
Produced a cellular response in proportion to the
change in concentration of the second messenger
Be degraded rapidly to ensure transiency in
signalling pathways
cAMP, cGMP, PI, Ca ion, protein kinase

ECF
Contents

Hormone
Receptor

Fig. Specificity and sensitivity of

hormone receptors

Cell types

Hormone + Receptor

Class

Receptor
Kinases

Receptor-Linked
Kinases

G-Protein Coupled
Ligand Gated
Receptors
Ion

Channels
Ligands

Insulin
Growth Hormone,
Peptides,
Growth Factors
Prolactin,
Neurotransmitters
Cytokines
prostaglandins

R
E

General
Structure

Protein Tyrosine or
Serine Kinase

Receptor Associated
Tyrosine Kinase

Neurotransmitters
Amino Acids

2 nd Messenger
(cAMP, IP3, Ion)

Ion

Cytoplasmic
Protein Kinases
Phosphorylation Mediated Actions

Non-Phosphorylation Mediated Actions

Fig. Four major classes of membrane receptors

exist for hormones and neurotransmitters

1 molecule of
signaling ligand
Each activated receptor protein
activates many molecules of G
protein, each of which in turn
activates an adenylate cyclase
molecule

receptor protein

G Protein
activated
adenylate cyclase

AMPLIFICATION

GTP
Each activated adenylate
cyclase molecule generates
many cAMP molecules

GTP

ATP

GTP

AMPLIFICATION
cAMP

Each cAMP molecule

activates 1 molecules
of protein kinase

Protein
kinase
Each kinase molecules
phosphorylates and
thereby activates many
copies enzyme X

Each copy of enzyme

X produces many
molecules of product

Fig. Amplification of
cellular signaling after
stimulation of a cAMP-

AMPLIFICATION

Enzyme X

AMPLIFICATION

Product of
enzyme X

Simplified model of insulin signaling

Van den Berghe, G. J. Clin. Invest. 2004;114:1187-1195

Nuclear receptors
Steroid receptor family

Protypical glucocorticoid receptor (GR)

Mineralocorticoid receptor (MR)
Androgen receptor (AR)
Progesteron receptor (PR)

Thyroid receptor family

Thyroid hormone receptor (TR)

Estrogen receptor (ER)
Retinoic acid receptor (RAR and RXR)
Vitamin D receptor (VDR)
Peroxisome proliferator-activated receptor (PPAR)

Exterior
Cytosol
Hsp90
GR

Nucleus

LBD

AD
DBD

D
LB

AD

Hormone

DBD

AD

DBD

LBD

Response
element

Fig. Model of hormone-dependent gene activation by

corticosteroid receptor (GR)
GR, glucocorticoid receptor; LBD, ligand binding domain; DBD, DNA-binding domains; HsP, heat
shock protein

TR
TRE

mRNA

Protein

Pol II
T3-responsive
gene

Differentiaton
Metabolism
Other effects
Of T3

Fig. Model of mediation of T3 action by nuclear thyroid hormone

receptors
TRE=thyroid hhor,ome-responsive element; Pol II = RNA polymerase II; a2=c-erbAa2, the non-T 3binding splice variant, can inhibit the effects of T3-bound TRs

Function of Hormones
Reproduction

Growth and development

Hormones

Maintenace of
internal environment

Energy production,
utilization and storage

Action 2
Action 1
Action 3

Action 2
Action 1

Hormone
Hormone
11

Action 3

Hormone
Hormone
22

Multihormonal
Multihormonal
process
Process

Hormone
Hormone
3
Action 1

Action 2

Action 3

Fig. Actions of hormones. A single hormone may act

independently or in concert with other hormones

Hormone actions
Single action
TSHThyroid hormone
ACTH Corticosteroid

As a concert
Protein/Fat Metabolism
Insulin
Vascular tone
Glucose homeostasis
Glucagon

Corticosteroid

Catecholamines

Two major types of control

of endocrine gland function
CNS input

Other
input

Varied input

Hypothalamus
Releasing hormone
Pituitary
Tropic hormone

Free-standing
endocrine
gland

Hormone

Peripheral gland
Hormone

Target

Target
Effect

Effect

FEEDBACK RELATIONSHIPS
Hypothalamus
TRH
Pituitary
TSH
Thyroid
T4
rT3 T3
Fig. A classic feedback system:
control of thyroid hormone release

Primary
failure of
target
Endocrine
organ

Normal
Low

TROPIC HORMONE LEVEL

High

Thyroid disease : 1. Subclinical hypothyroidism; 2. Subclinical hyperthyroidism

Autonomous
secretion of
tropic hormone
or resistance to
target gland
hormone action

Normal
range

Pituitary
failure
Low

Normal

Autonomous
secretion of
target
endocrine
organ

High

TARGET GLAND HORMONE LEVEL

Fig. Alteration in trophic and target organ hormone

pair their interpretation

Thyroid
dysfunction
Disease

Hormone levels

Primary
Hypofunction
Hyperfunction
Primary Subclinical
Hypofunction
Hyperfunction
Secondary/Tertiary
Hypofunction
Hyperfunction

TSH

Thyroxine

N
N

ENDOCRINE PATHOLOGY
1.
2.
3.
4.
5.

Subnormal hormone production

Hormone overproduction
Production of abnormal hormone
Disorder of hormone receptors
Abnormalities of hormone transport or
metabolism
6. Multiple hormone abnormalities
7. Benign or malignant tumors that produce
hormone

Hypofunction
Hyperfunction
Destruction
Block
Hyperplasia

Gland

Prohormone
Block
Stimulation

Tumor

Ectopic production
Iatrogenic

Hormone
Degraded

Block
Degraded

Antibodies
Antagonist

Antibodies
Receptor

Defect
Tissue damage
damage

Effector
Response

Stimulation
Tissue

Target cell
Fig. Causes of hypofunction and hyperfunction of
the endocrine system
The classic disorders of the endocrine system arise from states of exess or deficiency of hormones. However,
resistance to hormones also plays a major role in disease. The endocrinologist is also confronted with specific
tumors and other problems such as iatrogenic syndromes

Approach to the Patients with

Endocrine Disases

Evidence-based endocrinology
History & physical examination
Laboratory studies

Measurements of hormone level: basal levels

Plasma & urine assays
Free hormone levels
Indirect measurements of hormonal status
Provocative & suppression tests

Imaging studies
Biopsy procedures
Diagnosis of genetic disease

Assesment of Endocrine
Functions
Measurement of hormones
Individual hormones
Both arms of hormone feedback system
(e.g., T4 and TSH)

Dynamic endocrine testing

Stimulation test : hipofunction
Suppression test: hyperfunction