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Functional Human Physiology for the Exercise and Sport Sciences Chemical Messengers and the Endocrine System


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Title: Functional Human Physiology for the Exercise and Sport Sciences Chemical Messengers and the Endocrine System

Functional Human Physiologyfor the Exercise and
Sport Sciences Chemical Messengers and the
Endocrine System
  • Jennifer L. Doherty, MA, ATC
  • Department of Health, Physical Education, and
  • 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
  • Primary Endocrine Glands
  • Hypothalamus, Pituitary, Thyroid, Parathyroid,
    Adrenal, Pineal glands, Thymus, Pancreas, and
    Gonads ( Testes and Ovaries)
  • Secondary Endocrine Glands
  • Several organs contain endocrine tissue and
    produce hormones
  • Heart, kidneys, and others
  • The Endocrine System is integral in Intercellular

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

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Intercellular Communication
  • Indirect Communication through Chemical
  • Ligands (chemical messengers) bind to proteins
    (receptors) on the target cells
  • Chemical substances produced at one site cause an
    effect at a different site in the body.
  • Regulate metabolism, maintain homeostasis, and
    are essential for reproduction.
  • Binding between messenger and receptor results in
    a response in the target cell
  • Response is called Signal Transduction

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Chemical Messengers
  • Functional Classification (6)
  • Paracrines
  • Chemicals that communicate with neighboring cells
  • Autocrines
  • Chemicals that act on the same cell that secreted
  • Neurotransmitters
  • Chemicals released from neurons into the
    interstitial fluid

Chemical Messengers
  • Functional Classification (6) cont.
  • Hormones
  • Chemicals released from endocrine glands
  • Neurohormones
  • Chemicals released from a special class of
    neurons called neurosecretory cells
  • Cytokines
  • A wide range of chemical messengers released from
    a variety of cells, especially WBCs

Chemical Messengers
  • Chemical Classification (5)
  • 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
  • Open or close Channel-Linked, Enzyme-Linked, or
    G-Protein-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)

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  • Types of lipophobic messengers
  • Amino Acid Messengers
  • Function as neurotransmitters in the central
    nervous system
  • Examples include
  • Glutamate, Glycine, Gamma amino butyric acid
  • Most Amine Messengers
  • Substances derived from the amino acids
  • Examples include
  • Catecholamines (Both norepinephrine and
    epinephrine), secreted by neurons as
    neurotransmitters or by the adrenal medulla as
  • Peptide Messengers
  • Short chains of amino acids
  • 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
  • Control protein synthesis

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  • Types of lipophilic messengers
  • Steroid Messengers
  • Derived from cholesterol.
  • Cholesterol is made up of hydrogen, oxygen and
    carbon molecules and is most recognizable because
    of its 4-ring structure.
  • Examples include
  • Sex hormones
  • estrogen and testosterone
  • Some Amine Messengers
  • Derive from amino acids
  • 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
  • Changes the cell membrane permeability or
    membrane potential
  • Increases the production of proteins or
    regulatory molecules (enzymes) within the cell
  • Activates or deactivates enzymes
  • Increases secretory activity

Signal Transduction Mechanisms
  • Relationship Between Receptor Binding and the
    Magnitude of the Target Cell Response
  • Blood levels of the chemical messenger
  • The relative number of receptors for the chemical
  • Affinity (strength) of the union between the
    messenger and receptor

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Signal Transduction Mechanisms
  • Receptor Agonists and Antagonists
  • Agonists
  • Ligand binds to receptor and produces biological
  • Antagonists
  • Ligand binds to receptor, blocking the agonist
  • No biological response

Signal Transduction Mechanisms
  • Intracellular Receptor-Mediated Responses
  • Lipophilic messengers affect protein synthesis of
    the target cell by direct gene activation
  • 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

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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
  • 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

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Signal Transduction Mechanisms
  • G-Protein Linked Receptors
  • Involves the intracellular enzymes Cyclic AMP,
    Adenylate Cyclase, and Phosphodiesterase
  • Cyclic adenosine monophosphate (cAMP)
  • The best known second messenger
  • 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
  • Phosphodiesterase
  • cAMP is inactivated by another enzyme present in
    the cell, phospho-diesterase.

  • G-Protein second messenger systems
  • The hormone is the first messenger and it binds
    to receptor on the cell membrane, usually a G
  • The G-protein activates adenylate cyclase that
    generates cAMP from intracellular ATP (G protein
    is a transducer)
  • cAMP is the second messenger
  • It initiates a cascade of reactions by activating
    protein kinases which phosphorylate millions of
    proteins/enzymes, producing an amplification
  • 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.

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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
  • 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

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Specific Endocrine Glands and their Hormones
  • Control of Hormone Levels
  • Negative feedback
  • The concentration of each hormone in the body
    fluid is regulated precisely by negative feedback
  • In a negative feedback system, a gland is
    sensitive to the concentration of a substances it
  • 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.
  • Feedback systems occur when a hormone level or
    its effect is fed back to the gland.
  • 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
  • Produce responses in the same or other endocrine
  • For example, the hypothalamus secretes releasing
    hormones or inhibiting hormones to the anterior
    pituitary gland.
  • Increased release of particular anterior
    pituitary hormone into blood stream tells the
    hypothalamus to decrease secretion of releasing
  • Decreased secretion of the releasing hormones
    decreases the activity of the anterior pituitary.
  • Humoral stimuli
  • 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
  • Long-distance communication via the nervous and
    endocrine systems
  • Some endocrine glands secrete in response to
    neural stimuli or nerve control.
  • 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,

Primary Endocrine Glands
  • Main function is to secrete hormones
  • Hypothalamus and Pituitary Gland
  • Hypothalamus
  • Master control of one of the most important
    endocrine glands, the pituitary.
  • It contains centers for control of body
    temperature, appetite, thirst, blood nutrient
    concentrations, sexual behavior, and emotional
  • Functions as an important link between the
    nervous and endocrine systems.

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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).
  • Releasing hormones produced by the hypothalamus
    cause hormone release from the anterior
  • Inhibiting hormones produced by the hypothalamus
    slow or suppress the release of certain anterior
    pituitary hormones.

  • Hypothalamic control is regulated via negative
  • 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
  • Connect the hypothalamus to the anterior
  • Transports hypothalamic releasing and inhibiting
    hormones to the anterior pituitary gland.

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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
  • Promote cell growth and division (anabolic
    effect) by stimulating the uptake of amino acids
    and protein synthesis, while slowing protein
  • Increases the growth rate of skeleton and
    skeletal muscles during childhood and
  • 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
  • Prolactin inhibiting hormone (PIH) from the
  • Prolactin-releasing hormone (PRH) also from the
  • 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 prolactin-releasing factor promotes its

  • Melanocyte stimulating hormone (MSH)
  • The exact role in humans is unknown.
  • Tropic hormones
  • Regulate the activity of other endocrine glands.
  • There are no hypothalamic inhibiting factors
    associated with the tropic hormones, only
    releasing hormones.
  • Thyroid stimulating hormone (TSH) or thyrotropin
  • Stimulates normal development and secretory
    activity of the thyroid gland.
  • Stmulates synthesis and secretion of thyroid
  • Adrenocorticotropic hormone (ACTH)
  • Target organ as the adrenal cortex.
  • Stimulates release of corticosteroid hormones,
    especially cortisol from adrenal cortex.
  • Release is stimulated by corticotropin releasing
    hormone (CRH) from the hypothalamus.

  • Gonadotropins
  • Hormones that stimulate the hormonal functions of
    the gonads (ovaries and testes).
  • Follicle stimulating hormone (FSH)
  • Females
  • Stimulates the development of the follicle and
    egg in the ovaries and stimulates the follicles
    to secrete estrogen (female sex hormone). I
  • Males
  • This hormone known as interstitial cell
    stimulating hormone (ICSH)
  • Stimulates the interstitial cells of the testes
    to release testosterone and stimulates sperm cell
  • Luteinizing hormone (LH)
  • 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.
  • Males
  • Effects are not clinically important

Posterior pituitary gland hormones
  • 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
  • Decrease urine volume produced by the kidney (an
    antidiuretic) resulting in more fluid returned to
    the blood.
  • This increased blood volume produces increased
    blood pressure.
  • Also stimulates smooth muscle contraction in
    arterioles (small blood vessels) increasing blood

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Thyroid Hormones
  • Thyroxine (T4 )
  • 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
  • Increased production of oxidative enzymes and of
    Na/K pumps
  • Increased basal metabolic rate and metabolic heat
  • 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

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  • Calcitonin
  • A peptide hormone produced the thyroid gland.
  • Functions
  • 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.
  • Calcitonin works opposite (antagonist) of the
    parathyroid hormone in regulation of blood
    calcium levels

Parathyroid hormone (PTH)
  • A protein hormone secreted by the parathyroid
  • Functions as a second messenger to
  • Increase blood calcium and decrease blood
    phosphate by stimulating osteoclast activity
    and increasing bone resorption thus increasing
    blood calcium levels.
  • Release is stimulated by decreased blood calcium
  • Parathyroid hormone is the single most important
    regulator of calcium levels in adult humans.
  • Important for normal transmission of nerve
    impulses, muscle contraction, and blood
  • 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
  • Zona glomerulosa
  • produces aldosterone, a mineralocorticoid
  • Zona fasciculata
  • produces cortisol, the most abundant
  • Zona reticularis
  • produces the adrenal sex hormones, primarily the
    androgens and estrogens or the gonadocorticoids.

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  • 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
  • Mineralcorticoid
  • 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.
  • The effects of cortisol are
  • Glucose sparing effect
  • Stimulates metabolism of lipids, and proteins
  • Stimulates gluconeogenesis, by facilitating
    lipolysis and proteolysis for gluconeogenic
  • Provides resistance to stress by insuring
    adequate blood glucose levels for ATP production
    such as between meals, during starvation, during
    prolonged exercise, etc.
  • Anti-inflammatory effect
  • Decreases capillary permeability
  • Reduces histamine release
  • Stabilizes lysosomal membranes
  • In excess, cortisol slows connective tissue
    regeneration and may decrease immune function
  • 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 41 ratio.
  • At rest, catecholamines are secreted continuously
    in small amounts.
  • During stress, catecholamines produce the fight
    or flight response.

Fight or Flight Response
  • Increased heart rate and contractility (force of
    contraction) resulting in increased blood
  • Increased bronchodilation and respiration rate
  • Decreased digestive activity
  • Increased blood glucose levels
  • Increased fatty acid mobilization from adipose
  • 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

  • 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
  • Millions of small clusters of cells scattered
    throughout the pancreas.
  • Three distinct types of cells in the Islets of
  • 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.

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Hormones of the Islets of Langerhans
  • Insulin
  • A protein hormone produced by the beta cells of
    the pancreas.
  • Widespread metabolic effects
  • 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
  • Stimulating glycogenolysis, breakdown of glycogen
    to glucose in the liver
  • Stimulateing by gluconeogenesis
  • Stimulating the liver to release stored glucose
    to bloodstream
  • 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
  • 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
  • Thymopoietin and thymosin
  • Peptide hormones
  • Essential for normal development of T-
    lymphocytes directly affecting the immune

Secondary Endocrine Glands
  • Produce hormones in addition to other functions
  • Heart
  • Atrial Natriuretic Peptide (ANP)
  • Regulates sodium reabsorption by the kidneys
  • Kidneys
  • Erythropoietin
  • Stimulates red blood cell production in bone