The Endocrine System

Department of Physiology Diponegoro University Faculty of Medicine

 Introduction Thyroid
gland
Endocrine gland
The endocrine system assists the
nervous system with communication
and control of the body
The cells, tissues, and organs are
called endocrine glands Hormone secretion

▪ Ductless, secrete hormones to Endocrine

cell
bloodstream,
▪ Similar glands called paracrine and Blood flow (a)
Skin
autocrine glands that are quasi-
endocrine
Duct
Other glands that secrete substances
are the exocrine glands
▪Have ducts, deliver the products Exocrine
Exocrine gland
(sweat gland)
directly to a specific site cells
(b)
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 Endocrine System Major Endocrine Organs
• Controls numerous body
processes
• Growth and development
• Metabolism
• Reproduction
• Homeostasis

• Numerous organs and tissues

located throughout the body

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General Characteristics of the Endocrine System
The endocrine and nervous systems communicate
using chemical signals
• Neurons release neurotransmitters into a
synapse affecting postsynaptic cells
• Endocrine glands release hormones into the
bloodstream to specific target cell receptors

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 Nerve impulse

Neuron
Neurotransmitter Post-
transmits
released into synaptic
nerve
synapse cell responds
impulse

(a)

Target cells
(cells with hormone
Glandular receptors) respond
cells secrete to hormone
Bloodstream
hormone into
bloodstream
Hormones have no
effect on other cells

5
(b)
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 Endocrine vs Nervous Control

• Both share a role for control and

coordination throughout the body
• Should not be considered as separate entities

• Some endocrine glands respond to nervous stimuli

• Endocrine system maintains nervous system
• Both systems involve reflexes

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 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
Department of Physiology Diponegoro University Faculty of Medicine
 Hormones
▪ Hormones: cell to cell communication molecules
▪ Made in gland(s) or cells
▪ Transported by blood
▪ Distant target tissue receptors
▪ Activates physiological response
▪ Hormones –is a chemical secreted by a cell or group of
cells into the blood for transport to a distant target,
where it exerts its effect at very low concentrations
▪ Regulate the metabolic function of other cells
▪ Have lag times ranging from seconds to hours
▪ Tend to have prolonged effects
▪ Are classified as amino acid-based hormones, or
steroids
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Department of Physiology Diponegoro University Faculty of Medicine
 Hormone Action

▪ Hormones alter target cell activity by one of two

mechanisms
▪ Second messengers involving:
▪ Regulatory G proteins
▪ Amino acid–based hormones
▪ Direct gene activation involving steroid hormones

▪ The precise response depends on the type of the

target cell

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 Mechanism of Hormone Action

▪ Hormones produce one or more of the following

cellular changes in target cells
▪ Alter plasma membrane permeability
▪ Stimulate protein synthesis
▪ Activate or deactivate enzyme systems
▪ Induce secretory activity
▪ Stimulate mitosis

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 Types of Hormones
• Protein and peptide (at least 3 amino acids).
Amino acid based (Polypeptide hormone)
▪ most abundant, cell surface receptors
▪ thyroxine, peptide, and protein hormones
• Amine
▪ cell surface or intracellular receptors
▪ modified amino acid residues
• Steroid
▪ intracellular receptors
▪gonadal and adrenocortical hormones

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Department of Physiology Diponegoro University Faculty of Medicine
 Protein and Polypeptide Hormones:
Synthesis and Release

Peptide hormone
Department of Physiology Diponegoro synthesis,
University packaging,
Faculty and release
of Medicine
 Protein and Polypeptide Hormone Receptors

▪ Surface receptor
▪ Hormone binds
▪ Transduction
▪ Enzyme activation
▪ Open channels
▪ Second messenger
systems
▪ Synthesis
Department of Physiology Diponegoro University Faculty of Medicine Membrane receptors for peptide hormones
 Protein & Polypeptide Hormone Action:
cAMP Second Messenger

▪ 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
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 Protein & Polypeptide Hormone Action: cAMP
Second Messenger

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 Protein & Polypeptide Hormone Action:
PIP-Calcium

▪ 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
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 Protein/Polypeptide Hormone Action:
PIP-Calcium

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Amine Hormones

• Derivatives of single amino acid residues,

primarily TYROSINE
• Can behave either like peptides or steroids
• Receptors: Surface, Intracellular
• Small size, OH group, Benzine ring
• Examples: Thyroxin, Epinephrine
• Key characteristics:
• lipophilic
• carrier molecules required
• surface and intracellular receptors
• fast and slow acting
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 Amine Hormone Structures and Functions

Tyrosine-derived
Department of Physiology Diponegoro University Faculty of Medicineamine hormones
 Steroid Hormones: Structure and Action

▪ From cholesterol, lipophilic (not stored), enter target cell

Cytoplasmic or nuclear receptors (mostly)
▪ Function
▪ Activate DNA for protein synthesis
▪ Slower acting - genomic actions
▪ longer half-life
▪ specific protein carrier molecules
▪ Examples: cortisol, estrogen & testosterone

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 Steroid Hormones

▪ 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

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 Steroid Hormones Action

Steroid hormone action

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 Steroid Hormones: Structure and Action

Steroid hormones are derived from cholesterol

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 Hormone Target Cell Specificity

▪ 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
▪ These receptors may be intracellular or located on
the plasma membrane

Department of Physiology Diponegoro University Faculty of Medicine

 Target Cell Specificity

▪ Hormones circulate to all

tissues but only activate
cells referred to as target
cells
▪ “Lock and key” concept
▪ Target cells must have
specific receptors to
which the hormone binds
▪ These receptors may be
intracellular or located
on the plasma membrane

Department of Physiology Diponegoro University Faculty of Medicine

 Target Cell Specificity

▪ Examples of hormone
activity
▪ ACTH receptors are
only found on
certain cells of the
adrenal cortex
▪ Thyroxin receptors
are found on nearly
all cells of the body

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 Target Cell Activation
▪ 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

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 Hormone Concentrations in the Blood
▪ Hormones circulate in the blood in two forms –
free or bound
▪ Steroids and thyroid hormone are attached to plasma
proteins
▪ All others are unencumbered
▪ 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
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 Interaction of Hormones at Target Cells

▪ Three types of hormone interaction

▪ Permissiveness – one hormone cannot exert its
effects without another hormone being present
▪ Synergism – more than one hormone produces the
same effects on a target cell
▪ Antagonism – one or more hormones opposes the
action of another hormone

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More Impacts on Target Cells

▪ Synergism: multiple stimuli more than additive

▪ Cortisol +5
▪ Glucagon +10
▪ Epinephrine +20 (added = +35)
▪ Synergistic effect + 140

▪ Antagonism: glucagons opposes insulin

▪ Permissiveness: need 2nd hormone to get full
expression
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More Impacts on Target Cells - Synergism

Synergism
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 Control of Hormone Release

• Substrate control
- glucose regulating insulin release

• Nervous control
- pituitary hormones

• Trophic hormones
- released by the anterior pituitary

Department of Physiology Diponegoro University Faculty of Medicine

 Control of Hormone Release

• Trophic hormones •Nervous control • Substrate control

control
– Hypothalamus – Nervous system – Changing level
of substance
in plasma
– Anterior pituitary gland

Peripheral Endocrine Endocrine

endocrine gland gland
gland

Target cells Target cells Target cells

Action Action Action

(a) (b) (c)

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Endocrine Control: Three Levels of Integration

▪ Hypothalamic stimulation–from CNS

▪ Pituitary stimulation–from hypothalamic trophic
hormone
▪ Endocrine gland stimulation–from pituitary trophic
hormone

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Three Levels of Integration

: Hormones
Department of Physiology Diponegoro University of Medicine
Faculty of the hypothalamic-anterior pituitary pathway
 Control of Hormone Release

▪ Blood levels of hormones:

▪ Are controlled by negative feedback systems

▪ Vary only within a narrow desirable range

▪ Hormones are synthesized and released in response

to humoral, neural, and hormonal stimuli

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 Feedback control

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(-) Feedback Controls: Long & Short Loop Reflexes
Example:

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 Negative Feedback

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 Positive Feedback

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 Endocrine Reflex Pathways

▪ Stimulus
▪ Afferent signal
▪ Integration
▪ Efferent signal (the
hormone)
▪ Physiological action
▪ Negative feedback

Department of Physiology Diponegoro University Faculty of Medicine

 Humoral Stimuli
▪ Humoral stimuli – secretion of
hormones in direct response to
changing blood levels of ions and
nutrients
▪ Example: concentration of calcium
ions in the blood
▪ Declining blood Ca2+
concentration stimulates the
parathyroid glands to secrete PTH
(parathyroid hormone)
▪ PTH causes Ca2+ concentrations to
rise and the stimulus is removed
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 Hormonal Stimuli

▪ Hormonal stimuli – release

of hormones in response to
hormones produced by
other endocrine organs
▪ The hypothalamic
hormones stimulate the
anterior pituitary
▪ In turn, pituitary
hormones stimulate
targets to secrete still
more hormones
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 Adrenal-Pituitary
Axis
Hormone control

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 Neural Stimuli

▪ Neural stimuli – nerve

fibers stimulate hormone
release
▪ Preganglionic
sympathetic nervous
system (SNS) fibers
stimulate the adrenal
medulla to secrete
catecholamines

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 Nervous System Modulation
▪ The nervous system modifies the stimulation of
endocrine glands and their negative feedback
mechanisms
▪ The nervous system can OVERRIDE normal
endocrine controls
▪ For example, control of blood glucose levels
▪ Normally the endocrine system maintains blood
glucose
▪ Under stress, the body needs more glucose
▪ The hypothalamus and the sympathetic nervous
system are activated to supply ample glucose
Department of Physiology Diponegoro University Faculty of Medicine
 Multiple Stimuli for Hormone Release

▪ Stimuli
▪ Stretch
▪ Glucose
▪ Insulin levels
▪ Reflex
▪ Lower blood
glucose
▪ Reduces
stimulus
▪ Reduces insulin
release

Department of Physiology Diponegoro University Faculty of Medicine

Multiple Hormones Can Target a Cell/Tissue

▪ Growth H
▪ Somatomedins
▪ Thyroxin
▪ All have receptors
on many tissues
▪ Stimulate pathways
for growth
A complex endocrine pathway
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 Hormone metabolism
• Excretion by kidney
• Metabolism by liver
• Enzymes at target cell

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 Hormone metabolisme fail example:

Liver
cirrhosis

Estrogen
in male
increase

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Summary

Department of Physiology Diponegoro University Faculty of Medicine