The Endocrine System
Dr. Khalid Alregaiey
Learning Objectives
• List the general chemical categories of hormones
and give examples of hormones within each
category.
• Explain how different hormones can exert
synergistic, permissive, or antagonistic effects.
• Explain how hormone concentrations in the blood
are regulated
• Describe the mechanisms of actions of hormones
Endocrine System: Overview
• Endocrine system – the body’s second great
controlling system which influences metabolic
activities of cells by means of hormones
• Endocrine glands – pituitary, thyroid,
parathyroid, adrenal, pineal, and thymus
• The pancreas and gonads produce both hormones
and exocrine products
Endocrine System: Overview
• 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
Endocrine System: Overview
• THE NERVOUS SYSTEM exerts point-topoint 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.
Major Endocrine Organs
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
Hormones
• Hormones – chemical substances secreted by cells
into the extracellular fluids
• 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
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
Hormone Action
• Hormones alter target cell activity by one of two
mechanisms
• Cell membrane receptors:
• G Protein-coupled receptors
• Tyrosine kinase receptors
• Cytokines Receptors
• Cytoplasmic or nuclear receptors: Direct gene
activation involving steroid hormones
• The precise response depends on the type of the
target cell
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
Amino Acid-Based 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
Amino Acid-Based Hormone Action: cAMP
Second Messenger
Amino Acid-Based 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
Amino Acid-Based Hormone Action:
PIP-Calcium
Tyrosine Kinase Receptors (RTK)
Steroid and Thyroid 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
Steroid and Thyroid Hormones
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
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
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
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
• Others are unbound
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
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
Control of Hormone Release
• 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
Feedback control
• 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
Negative feedback
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
Humoral Stimuli
Neural Stimuli
• Neural stimuli – nerve
fibers stimulate hormone
release
• Preganglionic
sympathetic nervous
system (SNS) fibers
stimulate the adrenal
medulla to secrete
catecholamines
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
Hormonal Stimuli
Major Endocrine Organs: Pituitary (Hypophysis)
• Pituitary gland – two-lobed organ that secretes
nine major hormones
• Neurohypophysis – posterior lobe (neural tissue)
and the infundibulum
• Receives, stores, and releases hormones from
the hypothalamus
• Adenohypophysis – anterior lobe, made up of
glandular tissue
• Synthesizes and secretes a number of
hormones
Major Endocrine Organs: Pituitary
(Hypophysis)
Pituitary-Hypothalamic Relationships:
Posterior Lobe
• The posterior lobe is a downgrowth of
hypothalamic neural tissue
• Has a neural connection with the hypothalamus
(hypothalamic-hypophyseal tract)
• Nuclei of the hypothalamus synthesize oxytocin
and antidiuretic hormone (ADH)
• These hormones are transported to the posterior
pituitary
Pituitary-Hypothalamic Relationships:
Anterior Lobe
• The anterior lobe of the pituitary is an
outpocketing of the oral mucosa
• There is no direct neural contact with the
hypothalamus
Major Endocrine Organs: Pituitary
(Hypophysis)
Pituitary-Hypothalamic Relationships:
Anterior Lobe
Adenophypophyseal Hormones
• The six hormones of the adenohypophysis:
• Are abbreviated as GH, TSH, ACTH, FSH, LH,
and PRL
• Regulate the activity of other endocrine glands
• In addition, pro-opiomelanocortin (POMC):
• Has been isolated from the pituitary
• Is enzymatically split into ACTH, opiates, and
MSH
Activity of the Adenophypophysis
• The hypothalamus sends a chemical stimulus to
the anterior pituitary
• Releasing hormones stimulate the synthesis
and release of hormones
• Inhibiting hormones shut off the synthesis and
release of hormones
Hormones of the hypothalamus
1. Thyrotropin-releasing hormone (TRH), which
causes release of thyroid-stimulating hormone
2. Corticotropin-releasing hormone (CRH), which
causes release of adrenocorticotropin
3. Growth hormone–releasing hormone (GHRH),
which causes release of growth hormone, and
growth hormone inhibitory hormone (GHIH), alsocalled somatostatin,
which inhibits release of
growth hormone
4. Gonadotropin-releasing hormone (GnRH), which
causes release of the two gonadotropic hormones,
luteinizing hormone and follicle-stimulating
hormone
5. Prolactin inhibitory hormone (PIH), which causes
inhibition of prolactin secretion
Activity of the Adenophypophysis
• The tropic hormones that are released are:
• Thyroid-stimulating hormone (TSH)
• Adrenocorticotropic hormone (ACTH)
• Follicle-stimulating hormone (FSH)
• Luteinizing hormone (LH)
Gonadotropins
• Gonadotropins – follicle-stimulating hormone
(FSH) and luteinizing hormone (LH)
• Regulate the function of the ovaries and testes
• FSH stimulates gamete (egg or sperm)
production
• Absent from the blood in prepubertal boys and
girls
• Triggered by the hypothalamic gonadotropinreleasing hormone (GnRH) during and after
puberty
Functions of Gonadotropins
• In females
• LH works with FSH to cause maturation of the
ovarian follicle
• LH works alone to trigger ovulation (expulsion
of the egg from the follicle)
• LH promotes synthesis and release of estrogens
and progesterone
Functions of Gonadotropins
• In males
• LH stimulates interstitial cells of the testes to
produce testosterone
• LH is also referred to as interstitial cellstimulating hormone (ICSH)
Growth Hormone (GH)
• Produced by somatotropic cells of the anterior
lobe that:
• Stimulate most cells, but target bone and
skeletal muscle
• Promote protein synthesis and encourage the
use of fats for fuel
• Most effects are mediated indirectly by
somatomedins
Growth Hormone (GH)
• Antagonistic hypothalamic hormones regulate GH
• Growth hormone–releasing hormone (GHRH)
stimulates GH release
• Growth hormone–inhibiting hormone (GHIH)
inhibits GH release
Metabolic Action of Growth Hormone
• GH stimulates liver, skeletal muscle, bone, and
cartilage to produce insulin-like growth factors
• Direct action promotes lipolysis and inhibits
glucose uptake
Metabolic Action of Growth Hormone
Thyroid Stimulating Hormone (Thyrotropin)
• Tropic hormone that stimulates the normal
development and secretory activity of the thyroid
gland
• Triggered by hypothalamic peptide thyrotropinreleasing hormone (TRH)
• Rising blood levels of thyroid hormones act on the
pituitary and hypothalamus to block the release of
TSH
Adrenocorticotropic Hormone (Corticotropin)
• Stimulates the adrenal cortex to release
corticosteroids
• Triggered by hypothalamic corticotropinreleasing hormone (CRH) in a daily rhythm
• Internal and external factors such as fever,
hypoglycemia, and stressors can trigger the
release of CRH
Prolactin (PRL)
• In females, stimulates milk production by the
breasts
• Triggered by the hypothalamic prolactin-releasing
hormone (PRH)
• Inhibited by prolactin-inhibiting hormone (PIH)
• Blood levels rise toward the end of pregnancy
• Suckling stimulates PRH release and encourages
continued milk production
Physiology of posterior Pituitary gland
• Posterior pituitary hormones
• ADH also known as
Vasopressin
• Oxytocin
• These hormones are
synthesized in the neuron
cell bodies in the
hypothalamus and packed in
secretory vesicles with
neurophysin (carrier protein)
Posterior
PosteriorPituitary
pituitary Gland
gland
• Does not
synthesize
hormones
• Consists of axon
terminals of
hypothalamic
neurons
Antidiuretic Hormone
(ADH)
(vasopressin)
Synthesis of ADH
• It is synthesized as pre-prohormone and
processed into a nonapeptide
• ADH synthesized in the cell bodies of
hypothalamic neurons(supraoptic nucleus)
• ADH is stored in the posterior pituitary
Receptors of ADH (vasopressin)
• There are 2 types of receptors for ADH:
• V1
• V2
 V1 receptors mediate vasoconstriction
 V2 receptors are located in the principle cells in distal
convoluted tubule and collecting ducts in the kidneys
Mechanism of action of ADH: Antidiuresis
• ADH binds to V2 receptors on the principle cells of the
distal convoluted tubules and collecting ducts.
• Via adenylate cyclase/cAMP induces production of
specific proteins into the luminal membrane and
enhances permeability of cell to water.
• Increased membrane permeability to water permits
back diffusion of free water, resulting in increased
urine osmolality (concentrates urine).
Mechanism of action of ADH
Control of ADH Release
• Osmotic pressure:
• Osmoreceptors in the hypothalamus
• osmotic pressure  ADH secretion
•  osmotic pressure   ADH secretion
• Blood volume :
• Baroreceptor in carotid artery and aortic arch, and
Stretch receptors in left atrium
• blood pressure   ADH secretion
• blood pressure   ADH secretion
Function of ADH (vasopressin)
ADH
V1 receptor
Increased
Blood
Pressure
Oxytocin
Synthesis of Oxytocin
• Oxytocin is synthesized in the cell bodies of
hypothalamic neurons(paraventricular nucleus)
• Oxytocin is stored in the posterior pituitary
Functions of oxytocin
 Suckling during breast-feeding
o Contracts the myoepithelial cells of the alveoli

Childbirth (Parturition)
o In late pregnancy, uterine smooth muscle (myometrium)
becomes sensitive to oxytocin (positive feedback)
Summary of posterior pituitary hormones actions