Endocrinology - PowerPoint PPT Presentation

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Biol 155 Human Physiology ... Endocrinology – PowerPoint PPT presentation

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Title: Endocrinology

Major endocrine glands in the body
  • Peptide hormones largest, most complex, and most
    common hormones. Examples include insulin and
  • Steroid hormones lipid soluble molecules
    synthesized from cholesterol. Examples include
    gonadal steroids (e.g testosterone and estrogen)
    and adrenocortical steroids (e.g. cortisol and
  • Amines small molecules derived from individual
    amino acids. Include catecholamines (e.g.
    epinephrine produced by the adrenal medulla), and
    thyroid hormones.
  • Eicosanoids small molecules synthesized from
    fatty acid substrates (e.g. arachidonic acid)
    located within cell membranes

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  • ENDOCRINE Most common (classical) mode, hormones
    delivered to target cells by blood.
  • PARACRINE Hormone released diffuses to its
    target cells through immediate extracellular
  • Blood is not directly involved in the delivery.
  • AUTOCRINE Hormone released feeds-back on the
    cell of origin, again without entering blood
  • NEUROENDOCRINE Hormone is produced and released
    by a neuron, delivered to target cells by blood.

  • Only target cells, or cells that have specific
    receptors, will respond to the hormones
  • The strength of this response will depend on
  • Blood levels of the hormone
  • The relative numbers of receptors for that
    hormone on or in the target cells
  • The affinity (or strength of interactions) of the
    hormone and the receptor.

  • The affinity of hormones to their specific
    receptors is typically very high
  • The actual concentration of a circulating hormone
    in blood at any time reflects
  • Its rate of release.
  • The speed of its inactivation and removal from
    the body.

  • The half-life is the time required for the
    hormone to loose half of its original
    effectiveness (or drop to half of its original
  • The time required for hormone effects to take
    place varies greatly, from almost immediate
    responses to hours or even days.
  • In addition, some hormones are produced in an
    inactive form and must be activated in the target
    cells before exerting cellular responses.
  • In terms of the duration of hormone action, it
    ranges from about 20 minutes to several hours,
    depending on the hormone.

  • The synthesis and secretion of most hormones are
    usually regulated by negative feedback systems.
  • As hormone levels rise, they stimulate target
    organ responses. These in turn, inhibit further
    hormone release.
  • The stimuli that induce endocrine glands to
    synthesize and release hormones belong to one of
    the following major types
  • Humoral
  • Neural
  • Hormonal

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  • cAMP IP3

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Pituitary Gland
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The Master Gland
  • The pituitary has been called the Master gland
    in the body.
  • This is because most of the pituitary hormones
    control other endocrine glands

Hormones of the anterior pituitary
  • There are 6 main hormones which are secreted by
    the adenohypophysis
  • 1) Growth hormone (also known as somatotropin).
  • 2) Thyroid-stimulating hormone (also known as
  • 3) Adrenocorticotropic hormone (also known as
  • 4) Prolactin.
  • 5) Follicle-stimulating hormone.
  • 6) Luteinizing hormone.

Control of pituitary gland secretion
  • Secretion of each hormone by the adenohypophysis
    is controlled by neurohormones secreted by
    nerves in the hypothalamus.
  • In most cases there are two neurohormones
    controlling the secretion of a pituitary hormone.
    One which stimulates pituitary secretion and one
    which inhibits pituitary secretion.

  • Are hormones secreted by nerve cells. These are
    true hormones, since they are secreted into the
  • All are secreted by neurosecretory neurons in the
  • They are secreted into the hypophyseal portal
    system, which then carries the blood to the
    anterior pituitary.

Pituitary portal system
  • Arterioles break into capillaries in the
  • The axons of the neurosecretory cells form
    plexuses with these capillaries.
  • Downstream, the capillaries combine into a vein
    which carries the blood to the pars distalis.
  • The vein breaks into a capillary network which
    supplies all the cells of the anterior lobe.
  • Thus, the neurohormones are carried directly
    (well, sort of) from the hypothalamus to the

Portal system
Growth hormone (GH)
  • Growth hormone is secreted by somatotrophs.
  • GH is a protein hormone consisting of a single
    peptide chain of 191 amino acids.
  • GH secretion is stimulated by the secretion of
    Growth Hormone Releasing Hormone (GHRH) by the
  • GH secretion is inhibited by the secretion of
    somatostatin by the hypothalamus.
  • GH activates a tyrosine kinase receptor.

Functions of GH
  • GH has effects of every cell of the body, either
    directly or indirectly. Primarily, it decreases
    the uptake and metabolism of glucose. (Elevates
    plasma glucose)
  • Increases the breakdown of fat. (Increases the
    blood levels of fatty acids)
  • Increases the uptake of amino acids from the
    blood and increases protein synthesis in cell.
    (Decreases plasma amino acids)

Actions of GH on specific cell types
  • Muscle cells
  • Increases amino acid uptake
  • Increases protein synthesis
  • Decreases glucose uptake
  • Net result Increased Lean body mass

  • Chondrocytes
  • increases uptake of sulfur
  • increases chondroitin sulfate production
  • increases DNA, RNA synthesis
  • increases Protein synthesis
  • increases Amino acid uptake
  • increases Collagen synthesis
  • increases Cell size and number
  • Net result Increased Linear growth

  • Hepatocytes
  • Stimulates the production of somatomedins by the
  • These somatomedins directly regulate metabolic
    function in target cells. They are also called
    insulin-like growth factors, or IGFs.

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  • Adipocytes
  • Decreases glucose uptake
  • Increases lypolysis
  • Net result Decreased Adiposity

  • Other cell types in general
  • Increased protein synthesis
  • Increased DNA, RNA synthesis
  • Increased cell size and number
  • Net result Increased organ size
  • Increased organ function

Other considerations
  • GH has a short half-life of about 20 minutes.
    However, the IGFs are much longer lived (T1/2 of
    about 20 hours).

GH and Insulin actions are correlated
  • When there is ample dietary intake of proteins
    and carbohydrates, then amino acids can be used
    for protein synthesis and growth.
  • Under these conditions, both insulin and GH
    secretion are stimulated.
  • Net result Amino acids are shunted to protein
    synthesis and glucose is shunted to metabolism.
  • However, under conditions where only
    carbohydrates are ingested, insulin secretion is
    increased, but GH secretion is decreased.
  • Net result Both glucose AND amino acids are
    shunted to metabolism.

Pathophysiology of abnormal GH secretion
  • Hyposecretion
  • Pre-adolescents
  • Decreased GH secretion (or sensitivity) results
    in slow growth and delayed onset of sexual
    maturation. These children also tend to be
    slightly chubby.
  • Post-adolescents
  • Generally, no serious problems are associated
    with hyposecretion of GH in mature individuals.
    However, in very severe cases there can be
    progeria (rapid and premature aging).

  • Pre-adolescents (before closure of epiphyseal
  • Hypersecretion results in gigantism, where
    affected individuals grow extremely rapidly and
    become abnormally tall (even over 2.4 m). Body
    proportions remain relatively normal. Usually,
    there are cardiovascular complications later in

  • Post- adolescents (after epiphyseal closure).
  • Hypersecretion results in tissue enlargement.
    This is particularly true of the bones, which get
    heavier and thicker. They cannot elongate since
    the epiphyseal plates are closed. A common
    symptom is a coarsening of the facial features
    and enlargement of the hands and feet. This
    condition is known as acromegaly.

Treatments of GH secretion disorders
  • Hypersecretion is usually caused by a tumour in
    the pituitary gland. Treatment consists of
    surgical or radiation ablation of the tumour
  • Hyposecretion is usually treated in children by
    hormone replacement therapy. This is generally
    not required in adults, unless GH secretion is
    completely abolished.

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Prolactin (PRL)
  • Structurally, very similar to growth hormone
    (single peptide chain of 198 amino acids).
  • PRL is secreted by mammotrophs (also referred to
    as lactotrophs).
  • Secretion of PRL is also under dual control by
    the hypothalamus.

  • Primarily under inhibitory control. This means
    that if there is an injury to the hypophyseal
    portal system which blocks hypothalamic
    regulation of the pituitary gland, PRL levels
    increase. All other pituitary hormone levels
    decrease when this happens.
  • Dopamine is secreted by neuroendocrine cells in
    the hypothalamus and inhibits PRL release.
  • PRL release is stimulated by thyrotropin
    releasing hormone (TRH), vasoactive intestinal
    peptide (VIP) and at least one other as yet
    unidentified factor.
  • PRL activates a tyrosine kinase receptor.

Functions of PRL
  • In humans, the only effects of PRL so far
    identified are on reproduction and nursing.
  • PRL is important in stimulating differentiation
    of breast tissue during development.
  • Stimulates further development of mammary glands
    during pregnancy.
  • Stimulates milk production (lactation) after
  • PRL has a role in regulation of the female
    reproductive cycle. However, its precise role
    has not be delineated yet. Excess PRL secretion
    is know to block synthesis and release of
    gonadotropins, disrupting menstruation and
    causing infertility.
  • PRL also can regulate male fertility, but how it
    does so remains unclear.

Pathophysiology of PRL secretion
  • Hyposecretion is never seen. However,
    hyperprolactinemia (excess secretion of PRL) is a
    fairly common disorder. Symptoms in women
    usually include amenorrhea (cessation of
    menstruation), galactorrhea (abnormal lactation)
    and infertility. In men, infertility and
    galactorrhea are the most common symptoms.
  • Treatment usually consists of administration of a
    dopaminergic agonist, such as bromocriptine.

Thyroid Stimulating hormone (TSH)
  • TSH is a glycoprotein hormone composed of 2
    peptide chains a and b.
  • The a subunit is called unspecific because it
    is also incorporated into two other unrelated
    pituitary hormones (LH and FSH).
  • The b subunit contains the biologically active
    sites. However, it must be combined with the a
    subunit in order for the hormone to be active.

  • TSH secretion is controlled very tightly by the
  • TSH secretion is stimulated by Thyrotropin-releasi
    ng hormone (TRH). TRH is a tripeptide, meaning
    it is composed of three amino acids.
  • TRH secretion is stimulated by thermal and
    caloric signals in the brain.

Control of TSH secretion
  • Negative control of TSH secretion occurs in two
  • Triiodothyronien or T3 (which will be discussed
    later) feeds back on the hypothalamus to
    stimulate secretion of dopamine and somatostatin.
    These two factors both function as TSH-release
    inhibiting factors.
  • T3 can feed back directly onto the thyrotrophs to
    directly inhibit TSH secretion.

Function of TSH
  • TSH stimulates the follicular cells of the
    thyroid to induce a number of responses
  • TSH activates both the cAMP and PIP pathways
  • Increased cAMP
  • Increased Ca2i
  • TSH can stimulate both cell growth (of follicular
    cells) and secretion of T3 and thyroxine ( T4 ).

Adrenocorticotropic hormone (ACTH)
  • ACTH is a single peptide chain which is
    relatively small (30 amino acids).
  • ACTH secretion is primarily under stimulatory
    control (i.e. there isnt an ACTH-release
    inhibitory factor).
  • ACTH secretion is stimulated by corticotropin
    releasing hormone (CRH).
  • CRH secretion can be stimulated by a large number
    of factors, most of which would be considered
    stress factors.
  • Examples infection, trauma, sleep cycle,
    anxiety, depression and others. (Just remember

Functions of ACTH
  • ACTH stimulates the adrenal gland to secrete
  • ACTH levels are associated with the sleep cycle.
  • ACTH stimulates the cAMP pathway in
    adrenocorticol cells.
  • ACTH can directly inhibit CRH secretion (negative

Follicular-Stimulating hormone (FSH) Luteinizing
Hormone (LH)
  • These are generally grouped together and called
  • Gonadotropins are secreted by the gonadotrophs,
    which synthesize and secrete both LH and FSH.
  • Both LH and FSH are peptide hormones.
  • Secretion of gonadotropins is mainly under
    positive control.
  • Hypothalamus secretes gonadotropin-releasing
    hormone (GnRH) which stimulates gonadotrophs to
    secrete both LH and FSH.

Functions of LH and FSH
  • LH and FSH stimulate secretion of the sex
    steroids by the gonads. Mainly estrogen in women
    and testosterone in men.
  • FSH also stimulates gonadal release of inhibin,
    which serves as a negative feedback factor to
    block release of FSH by pituitary.
  • LH and FSH stimulate the gonadal release of
    activin, which can have positive feedback on
    gonadotropin secretion by the pituitary.
  • Gonadal secretion of estrogen and testosterone
    can negatively feedback on both the hypothalamus,
    to reduce GnRH secretion, and the gonadotrophs
    directly, to reduce gonadotropin secretions.

Hormones of the posterior pituitary
  • Remember that the neurohypophysis serves as a
    storage organ for hormones produced by
    neurosecretory cells in the hypothalamus.
  • There are two hormones secreted by the
  • 1) antidiuretic hormone (ADH)
  • 2) oxytocin
  • Both hormones are peptide hormones containing 9
    amino acid residues.
  • They differ in only 2 amino acids, but have very
    different functions.
  • Both activate the PIP pathway in the target cells.

  • Term diuresis ö means production of urine.
  • ADH inhibits urine production, i.e. conserves
    water in the body.
  • Main target for ADH are the cells in the kidney
    which reabsorb water (will be covered in detail
    in the section on renal physiology).
  • ADH secretion is stimulated by either an increase
    in the osmotic concentration of the blood, or by
    a decrease in blood volume
  • usually sensed by a decrease in blood pressure.

  • Secretion of ADH causes retention of water, which
    will tend to counteract both an increase in
    blood concentration and/or decrease in blood
  • cannot overcome serious blood loss.
  • Conversely, excess consumption of water will have
    two effects
  • increase blood volume (and pressure).
  • decrease blood concentration.
  • Under these conditions ADH secretion is
  • This results in formation of more urine, which is
    usually fairly dilute.
  • Blood loses water and thus volume.

  • Release of oxytocin is under neural control (like
    with ADH).
  • However, unlike ADH, the release of oxytocin is
    largely controlled by emotional state.
  • Oxytocin is required for nursing.
  • Principally know as the milk letdown factor.
  • It is secreted within seconds of the onset of
  • Sensory receptors in the nipples generate
    afferent impulses that stimulate the
    hypothalamus, triggering oxytocin secretion.
  • Can actually be secreted in response to auditory
    input, i.e. in nursing mothers in response to
    hearing their babies cry.
  • Oxytocin specifically stimulates certain smooth
    muscles to contract.
  • Primarily those of the reproductive tract and
    mammary glands.

Effects of Oxytocin
  • Oxytocin stimulation at low doses causes rhythmic
    contractions of the uterus.
  • ö Oxytocin stimulation at high dose causes
    sustained tetanic uterine contractions.
  • ö Oxytocin is often used to induce labour.
  • ö It is now generally believed that oxytocin
    believed that oxytocin produced by the fetus
    plays a critical role in labour.
  • ö Oxytocin is also used to stop post-partum

  • The number of oxytocin receptors in uterine
    smooth muscles increases towards the end of
  • Oxytocin affects smooth muscle cells in uterus
    and vagina of non-pregnant women.
  • There is clear evidence that oxytocin is involved
    in sexual arousal and orgasm in both men and
  • What role it plays in men is unknown. However,
    it may play a strong role in reinforcing the
  • The role in women is only slightly better known.
  • Oxytocin is secreted in response to vaginal
    distention during intercourse.
  • Oxytocin is also secreted in response to
    stimulation of the nipples.

Emotional considerations
  • Oxytocin secretion during sexual intercourse
    probably serves to reinforce the male-female
  • Often referred to as the the cuddle hormone or
    the love hormone in the popular press.
  • Secretion of oxytocin during and after labour may
    play an important role in the formation of the
    mother-child pair-bond.
  • Oxytocin secreted during suckling may serve to
    reinforce this pair-bond.
  • Recent studies with knock out mice has shown that
    oxytocin is critical in initiating and
    maintaining maternal care.
  • Oxytocin secreted in response to suckling can
    cause uterine contractions which may play a role
    in the recovery of uterine muscle tone after
    pregnancy and may serve to shrink the uterus back
    to normal.
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