Download The Endocrine System - Florida International University

Functional Human Physiology
for the Exercise and Sport Sciences
Chemical Messengers and the Endocrine System
Jennifer L. Doherty, MA, ATC
Department of Health, Physical Education, and
Recreation
Florida International University
The Endocrine System
 Endocrine control of cell function
 Depends upon the secretion and action of chemical
messengers or hormones
 Directly linked to the autonomic nervous system
 Endocrine glands
 Ductless glands that release their secretory products
(hormones) directly into the extra-cellular fluid.
 Hormones then diffuse into capillaries and are carried
throughout the body in the blood.
 Specific Endocrine Glands
1) Primary Endocrine Glands
 Hypothalamus, Pituitary, Thyroid, Parathyroid, Adrenal,
Pineal glands, Thymus, Pancreas, and Gonads ( Testes
and Ovaries)
2) Secondary Endocrine Glands
 Several organs contain endocrine tissue and produce
hormones
 Heart, kidneys, and others
 The Endocrine System is integral in
Intercellular Communication
Intercellular Communication
 Direct Communication through Gap Junctions
 Connexins (plasma membrane proteins) link adjacent
cells forming connexons
 Connexons form channels that allow ions or small
molecules to pass directly from one cell to another
Intercellular Communication
 Indirect Communication through Chemical
Messengers
 Ligands (chemical messengers) bind to proteins
(receptors) on the target cells
1) Chemical substances produced at one site cause an effect at
a different site in the body.
2) Regulate metabolism, maintain homeostasis, and are
essential for reproduction.
 Binding between messenger and receptor results in
a response in the target cell
1) Response is called Signal Transduction
Chemical Messengers
 Functional Classification (6)
 Paracrines
1) Chemicals that communicate with neighboring cells
 Autocrines
1) Chemicals that act on the same cell that secreted them
 Neurotransmitters
1) Chemicals released from neurons into the interstitial
fluid
Chemical Messengers
 Functional Classification (6) cont.
 Hormones
1) Chemicals released from endocrine glands
 Neurohormones
1) Chemicals released from a special class of neurons
called neurosecretory cells
 Cytokines
1) A wide range of chemical messengers released from a
variety of cells, especially WBCs
Chemical Messengers
 Chemical Classification (5)
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Amino Acids (Lypophobic)
Amines (Lypophobic)
Peptides (Lypophobic)
Steroids (Lypophilic)
Eicosanoids (Lypophilic)
Chemical Messengers
 Lypophobic messengers
 Water-soluble (hydrophilic)
 Pass through the cell membrane
 Function to
1) Open or close Channel-Linked, Enzyme-Linked, or GProtein-Linked Receptors
 Altering the permeability of the cell membrane leading to
depolarization or hyperpolarization
 Activate membrane bound enzymes
 Activate the second messenger system (more later)
 Types of lipophobic messengers
 Amino Acid Messengers
1) Function as neurotransmitters in the central nervous system
2) Examples include
 Glutamate, Glycine, Gamma amino butyric acid (GABA)
 Most Amine Messengers
1) Substances derived from the amino acids
2) Examples include:
 Catecholamines (Both norepinephrine and epinephrine), secreted
by neurons as neurotransmitters or by the adrenal medulla as
hormones
 Peptide Messengers
1) Short chains of amino acids
2) Examples include:
 Insulin, oxytocin, antidiuretic hormone (ADH)
Chemical Messengers
 Lipophilic messengers
 Fat loving (hydrophobic)
 Do not pass through the cell membrane
 Bind with receptors in the cytosol or nucleus
of the target cell
 Function
1) Control protein synthesis
 Types of lipophilic messengers
 Steroid Messengers
1) Derived from cholesterol.
 Cholesterol is made up of hydrogen, oxygen and carbon
molecules and is most recognizable because of its 4-ring
structure.
2) Examples include:
 Sex hormones
 estrogen and testosterone
 Some Amine Messengers
1) Derive from amino acids
2) Thyroid hormones
 Thyroxine and triiodothyronine
Signal Transduction Mechanisms
 Binding between a messenger and a receptor
resulting in a response in the target cell
 Produces (one or more) of four typical
responses:
1) Changes the cell membrane permeability or membrane
potential
2) Increases the production of proteins or regulatory
molecules (enzymes) within the cell
3) Activates or deactivates enzymes
4) Increases secretory activity
Signal Transduction Mechanisms
 Relationship Between Receptor Binding and
the Magnitude of the Target Cell Response
1) Blood levels of the chemical messenger
2) The relative number of receptors for the chemical
messenger
3) Affinity (strength) of the union between the messenger
and receptor
Signal Transduction Mechanisms
 Receptor Agonists and Antagonists
 Agonists –
1) Ligand binds to receptor and produces biological
response
 Antagonists –
1) Ligand binds to receptor, blocking the agonist
2) No biological response
Signal Transduction Mechanisms
 Intracellular Receptor-Mediated Responses
1) Lipophilic messengers affect protein synthesis of the
target cell by direct gene activation
2) Usually involves steroid and some amine (thyroid
hormones) messengers
 These chemical messengers are lipid soluble. Lipids make up
most of the cell membrane so they readily diffuse through the cell
membrane.
 Once inside the cell, the steroid messenger combines with a
protein receptor usually located in the nucleus.
 A messenger-receptor complex interacts with chromatin in the
nucleus of cell and triggers transcription of specific genes
causing production of specific mRNA for synthesis of new
proteins
Signal Transduction Mechanisms
 Membrane-Bound Receptor Mediated Responses
 Binding of a chemical messenger or ligand to a
membrane-bound receptor initiates a chain of events
inside the cell that changes the cell's activity or
metabolism.
 Involves the amines (catecholamines), peptides, and
amino acid (lipophobic) messengers
1) These messengers are not soluble in lipids thus, they
cannot diffuse through the cell membrane and bind to
intracellular receptors.
 The messengers act through receptor proteins at the
external surface of the cell membrane and depend on
second messengers inside the cell to mediate the cellular
response to the chemical messenger.
Signal Transduction Mechanisms
 G-Protein Linked Receptors
 Involves the intracellular enzymes Cyclic AMP,
Adenylate Cyclase, and Phosphodiesterase
1) Cyclic adenosine monophosphate (cAMP)
 The best known second messenger
2) Adenylate cylase
 Cyclic AMP is synthesized in the cell from ATP via the
action of an enzyme attached to the inner surface of the
plasma membrane, adenylate cyclase.
3) Phosphodiesterase
 cAMP is inactivated by another enzyme present in the cell,
phospho-diesterase.
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G-Protein second messenger systems:
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The hormone is the first messenger and it binds to receptor on the cell
membrane, usually a G protein.
The G-protein activates adenylate cyclase that generates cAMP from
intracellular ATP (G protein is a transducer)
cAMP is the second messenger
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It initiates a cascade of reactions by activating protein kinases which
phosphorylate millions of proteins/enzymes, producing an amplification
effect.
Phosphorylation activates some proteins, but deactivates others. It is
like an on/off switch thus, cAMP can lead to many different
physiological responses.
Different cells contain different proteins so that cAMP is able to
produce different effects in different cells often with several different
actions in one cell at the same time.
cAMP is rapidly degraded by phosphodiesterase. This turns off the
cellular response, unless new hormone molecules continue to bind to
the membrane-bound receptor. There are other known second
messengers, cAMP is the best understood.
Signal Amplification in Chemical
Messenger Systems
 The ability of small changes in the
concentration of a chemical messenger to
elicit marked responses in target cells
 A single kinase enzyme can catalyze thousands
of reactions
 As the reaction cascades through enzymes, one
intermediately after another, the number of
product molecules increases dramatically.
 For example, one kinase enzyme can activate
many G-proteins producing thousands of cAMP
molecules
Specific Endocrine Glands and their
Hormones

Control of Hormone Levels
 Negative feedback
1) The concentration of each hormone in the body fluid is regulated
precisely by negative feedback systems.
2) In a negative feedback system, a gland is sensitive to the
concentration of a substances it regulates.
 When the concentration of the regulated substance reaches a certain
concentration, it inhibits the gland. As the gland secretes less hormone,
the controlled substance also decreases.
3) Feedback systems occur when a hormone level or its effect is fed
back to the gland.
4) The endocrine gland then responds in a manner that will return the
system to homeostasis.
 For example:
 Increased blood glucose concentrations stimulate insulin secretion by
the pancreas. Insulin stimulates glucose uptake by cells decreasing
the blood glucose concentration and inhibiting insulin secretion.

Three types of stimuli affect endocrine glands

Hormonal stimuli
1) Produce responses in the same or other endocrine glands.
 For example, the hypothalamus secretes releasing hormones or inhibiting
hormones to the anterior pituitary gland.
2) Increased release of particular anterior pituitary hormone into blood stream
tells the hypothalamus to decrease secretion of releasing hormones.
3) Decreased secretion of the releasing hormones decreases the activity of the
anterior pituitary.

Humoral stimuli
1) Refers to blood and other body fluids. This term refers to chemical changes
in the blood that can influence endocrine gland activity.
 For example, changes in blood glucose concentration produces changes
in insulin secretion by the pancreas.

Neural stimuli
1) Long-distance communication via the nervous and endocrine systems
2) Some endocrine glands secrete in response to neural stimuli or nerve
control.
3) Neural stimuli results from nerve fibers signaling hormonal release from a
gland.
 For example, the sympathetic nervous system stimulates the adrenal
medulla to release catecholamines during periods of stress such as,
exercise.
Primary Endocrine Glands
 Main function is to secrete hormones
 Hypothalamus and Pituitary Gland
 Hypothalamus
1) Master control of one of the most important endocrine
glands, the pituitary.
2) It contains centers for control of body temperature,
appetite, thirst, blood nutrient concentrations, sexual
behavior, and emotional state.
3) Functions as an important link between the nervous and
endocrine systems.
Anterior Pituitary Gland
 Controlled by the hypothalamus.
 The hypothalamus controls the secretory activity of the
anterior pituitary by producing releasing hormones (RH)
and inhibiting hormones (IH).
1) Releasing hormones produced by the hypothalamus cause
hormone release from the anterior pituitary.
2) Inhibiting hormones produced by the hypothalamus slow or
suppress the release of certain anterior pituitary hormones.
 Hypothalamic control is regulated via negative
feedback
 When blood concentration of a particular hormone
rises to a certain level, the hypothalamus either
decreases production of releasing hormone or
produces inhibiting hormone.
 Hypophyseal portal veins
1) Connect the hypothalamus to the anterior pituitary
2) Transports hypothalamic releasing and inhibiting
hormones to the anterior pituitary gland.
Anterior Pituitary Hormones
 Growth Hormone (GH)
 Protein hormone with target tissues throughout the body
(bones and muscles being the primary target cells).
 General effect of growth hormone
1) Promote cell growth and division (anabolic effect) by
stimulating the uptake of amino acids and protein synthesis,
while slowing protein catabolism.
 Increases the growth rate of skeleton and skeletal muscles during
childhood and adolescence.
 In adults, growth hormone helps maintain muscle and bone size
and promote tissue repair. It affects growth in target cells
indirectly, through proteins called somatomedins.
 Prolactin
 A protein hormone that initiates and maintains milk
secretion by the mammary glands in women.
 Regulated by
1) Prolactin inhibiting hormone (PIH) from the hypothalamus
2) Prolactin-releasing hormone (PRH) also from the
hypothalamus
3) Normally, prolactin inhibiting hormone predominates over
prolactin-releasing hormone (PRH) which suppresses milk
production. Prolactin release-inhibiting factor from the
hypothalamus restrains secretion of prolactin, while prolactinreleasing factor promotes its secretion.
 Melanocyte stimulating hormone (MSH)
 The exact role in humans is unknown.
 Tropic hormones
1) Regulate the activity of other endocrine glands.
2) There are no hypothalamic inhibiting factors associated with
the tropic hormones, only releasing hormones.
 Thyroid stimulating hormone (TSH) or thyrotropin
1) Stimulates normal development and secretory activity of the
thyroid gland.
2) Stmulates synthesis and secretion of thyroid hormones.
 Adrenocorticotropic hormone (ACTH)
1) Target organ as the adrenal cortex.
2) Stimulates release of corticosteroid hormones, especially
cortisol from adrenal cortex.
3) Release is stimulated by corticotropin releasing hormone
(CRH) from the hypothalamus.
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Gonadotropins
 Hormones that stimulate the hormonal functions of the gonads
(ovaries and testes).
 Follicle stimulating hormone (FSH)
1) Females
 Stimulates the development of the follicle and egg in the ovaries and
stimulates the follicles to secrete estrogen (female sex hormone). I
2) Males
 This hormone known as interstitial cell stimulating hormone (ICSH)
 Stimulates the interstitial cells of the testes to release testosterone and
stimulates sperm cell production.

Luteinizing hormone (LH)
1) Females
 Stimulates the maturation of the egg and its release from the ovary. This
includes ovulation or expulsion of the egg from the follicle, development
of the corpus luteum, release of the ovarian hormones estrogen and
progesterone.
2) Males
 Effects are not clinically important
Posterior pituitary gland hormones
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Oxytocin
 A protein hormone with two target tissues, the uterus and
breast.
 During childbirth, it stimulates the smooth muscle contractions
in the walls of uterus. Also, stimulates ejection of milk from
breast glands during lactation in response to the mechanical
stimulation from suckling infant.
 Example of a positive feedback mechanism
 Antidiuretic hormone (ADH)
 Also called vasopressin
 Effects of antidiuretic hormone
1) Decrease urine volume produced by the kidney (an antidiuretic)
resulting in more fluid returned to the blood.
2) This increased blood volume produces increased blood pressure.
3) Also stimulates smooth muscle contraction in arterioles (small blood
vessels) increasing blood pressure.
Thyroid Hormones
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Thyroxine (T4 )
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Accounts for almost 95% of circulating thyroid hormone,
although T3 is the more active form
Triiodothyronine (T3)
T3 and T4 function to:
 Stimulate cellular metabolism
1)
2)
3)
4)
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Increased production of oxidative enzymes and of Na+/K+ pumps
Increased basal metabolic rate and metabolic heat production
Increased heart rate and force of contraction
Increased blood pressure from up-regulation of catecholamine
receptors
The thyroid hormones are important in normal tissue growth
and development, maturation of the nervous system
 Calcitonin
 A peptide hormone produced the thyroid gland.
 Functions
1) Lower the blood calcium levels by inhibiting osteoclasts
and stimulating osteoblasts.
 Bone-sparing effect
 Secretion of calcitonin is stimulated when blood calcium
concentration is high such as immediately after a meal.
2) Calcitonin works opposite (antagonist) of the
parathyroid hormone in regulation of blood calcium
levels
Parathyroid hormone (PTH)
 A protein hormone secreted by the parathyroid
glands
 Functions as a second messenger to
1) Increase blood [calcium] and decrease blood [phosphate] by
stimulating osteoclast activity and increasing bone resorption
thus increasing blood calcium levels.
2) Release is stimulated by decreased blood calcium levels
 Parathyroid hormone is the single most important
regulator of calcium levels in adult humans.
1) Important for normal transmission of nerve impulses, muscle
contraction, and blood clotting.
2) Abnormalities of blood calcium levels result in depression of
the nervous system, abnormal reflexes, weak muscles,
twitches, and formation of kidney stones
Hormones of the Adrenal Cortex
 The adrenal cortex can be divided into three
zones that produce different types of
corticosteroid hormones.
 From superficial to deep:
1) Zona glomerulosa
 produces aldosterone, a mineralocorticoid
2) Zona fasciculata
 produces cortisol, the most abundant glucocorticoid
3) Zona reticularis
 produces the adrenal sex hormones, primarily the
androgens and estrogens or the gonadocorticoids.
Corticosteroids
 The collective term for the steroid hormones
secreted from the adrenal cortex that are essential
for life.
 The corticosteroids include the mineralcorticoids,
glucocorticoids, and the gonadocorticoids.
 Mineralcorticoid
1) Aldosterone
 Functions to maintain water and electrolyte homeostasis,
especially blood sodium and potassium levels by stimulating
sodium reabsorption (conservation) and potassium excretion by
the kidneys.
 Sodium is returned to the blood (with water) producing decreased
urine volume, increased blood volume, and increased blood
pressure.
 Glucocorticoid
 Cortisol, the most abundant.
1) The effects of cortisol are:
2) Glucose sparing effect
 Stimulates metabolism of lipids, and proteins
 Stimulates gluconeogenesis, by facilitating lipolysis and
proteolysis for gluconeogenic precursors
 Provides resistance to stress by insuring adequate blood glucose
levels for ATP production such as between meals, during
starvation, during prolonged exercise, etc.
3) Anti-inflammatory effect:
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Decreases capillary permeability
Reduces histamine release
Stabilizes lysosomal membranes
In excess, cortisol slows connective tissue regeneration and may
decrease immune function
4) Regulated by adrenocorticotropic hormone (ACTH) from the
anterior pituitary.
Hormones of the Adrenal Medulla
 Catecholamines
 Production and secretion is regulated by the
sympathetic division of autonomic nervous
system.
 Epinephrine (epi) and norepinephrine (NE) are
secreted in a 4:1 ratio.
1) At rest, catecholamines are secreted continuously in
small amounts.
2) During stress, catecholamines produce the fight or flight
response.
Fight or Flight Response
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Increased heart rate and contractility (force of contraction)
resulting in increased blood pressure
Increased bronchodilation and respiration rate
Decreased digestive activity
Increased blood glucose levels
Increased fatty acid mobilization from adipose tissue
Rerouting of blood flow to essential organs so that blood
vessels to the skin and kidneys are constricted while those to
the brain, skeletal muscles, lungs and heart dilate
The effects of epinephrine and norepinephrine are similar
however, the response actually generated at target cells
depends on the type of receptor available
Pancreas
 Located in the abdominal cavity posterior and
inferior to the stomach.
 Both endocrine and endocrine functions
 Exocrine (acinar) cells produce digestive enzymes
 Endocrine cells are the Islets of Langerhans
1) Millions of small clusters of cells scattered throughout the
pancreas.
2) Three distinct types of cells in the Islets of Langerhans:
 Alpha cells that secrete glucagon
 Beta cells that secrete insulin, comprise about 70% of islet cells
 Delta cells that secrete somatostatin, the same growth hormone
inhibiting hormone produced by hypothalamus. The physiological
function in the pancreas is probably to inhibit secretion of both
insulin and glucagon. This hormone will not be discussed further.
Hormones of the Islets of Langerhans
 Insulin
 A protein hormone produced by the beta cells of
the pancreas.
 Widespread metabolic effects:
1) Primary effect is to decrease blood glucose levels by:
 Stimulating glucose uptake by muscle cells (cardiac and
skeletal)
 Stimulating storage of excess carbohydrates as adipose
tissue
 Stimulating glycogenesis, formation of glycogen from
glucose in muscle and liver
 Inhibiting gluconeogenesis in liver
 Glucagon
 A polypeptide hormone produced by the alpha
cells of the Islets of Langerhans.
 Primary effect is to increase blood glucose levels
by
1) Stimulating glycogenolysis, breakdown of glycogen to
glucose in the liver
2) Stimulateing by gluconeogenesis
3) Stimulating the liver to release stored glucose to
bloodstream
4) Stimulates lipolysis for gluconeogenic precusors
Regulation of Insulin and Glucagon Secretion
 Negative feedback mechanism
 Insulin and glucagon are antagonists
regulated by changes in blood glucose
levels
 Insulin secretion is stimulated by high blood
glucose levels
 Glucagon secretion is stimulated by low blood
glucose levels
Thymus gland
 Located in the thoracic cavity, deep to the sternum.
 Atrophies with age
 Large in infants and children and decreases in size
throughout adulthood. By old age, it is composed
primarily of fatty and fibrous connective tissue.
 Hormones of the thymus gland
 Thymosins
1) Thymopoietin and thymosin
 Peptide hormones
 Essential for normal development of T- lymphocytes directly
affecting the immune response
Secondary Endocrine Glands
 Produce hormones in addition to other
functions
 Heart
1) Atrial Natriuretic Peptide (ANP)
 Regulates sodium reabsorption by the kidneys
 Kidneys
1) Erythropoietin
 Stimulates red blood cell production in bone marrow