The Endocrine System

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Chapter 18

• The Endocrine System
• Lecture Outline

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Chapter 18The Endocrine System

• The nervous and endocrine systems act as a
  coordinated interlocking supersystem, the
  neuroendocrine system.
• The endocrine system controls body activities by
  releasing mediator molecules called hormones.
• hormones released into the bloodstream travel
  throughout the body
• results may take hours, but last longer
• The nervous system controls body actions through
  nerve impulses.
• certain parts release hormones into blood
• rest releases neurotransmitters excite or inhibit
  nerve, muscle gland cells
• results in milliseconds, brief duration of
  effects

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NERVOUS and ENDOCRINE SYSTEM

• The nervous system causes muscles to contract or
  glands to secrete. The endocrine system affects
  virtually all body tissues by altering
  metabolism, regulating growth and development,
  and influencing reproductive processes.
• Parts of the nervous system stimulate or inhibit
  the release of hormones.
• Hormones may promote or inhibit the generation of
  nerve impulses.
• Table 18.1 compares the characteristics of the
  nervous and endocrine systems.

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General Functions of Hormones

• Help regulate
• extracellular fluid
• metabolism
• biological clock
• contraction of cardiac smooth muscle
• glandular secretion
• some immune functions
• Growth development
• Reproduction
• Hormones have powerful effects when present in
  very low concentrations.

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Endocrine Glands Defined

• Exocrine glands
• secrete products into ducts which empty into body
  cavities or body surface
• sweat, oil, mucous, digestive glands
• Endocrine glands
• secrete products (hormones) into bloodstream
• pituitary, thyroid, parathyroid, adrenal, pineal
• other organs secrete hormones as a 2nd function
• hypothalamus, thymus, pancreas,ovaries,testes,
  kidneys, stomach, liver, small intestine, skin,
  heart placenta

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Hormone Receptors

• Hormones only affect target cells with specific
  membrane proteins called receptors

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Hormone Receptors

• Although hormones travel in blood throughout the
  body, they affect only specific target cells.
• Target cells have specific protein or
  glycoprotein receptors to which hormones bind.
• Receptors are constantly being synthesized and
  broken down.
• Synthetic hormones that block the receptors for
  particular naturally occurring hormones are
  available as drugs. (Clinical Application)

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Regulation of Hormone Receptors

• Receptors are constantly being synthesized
  broken down
• range of 2000-100,000 receptors / target cell
• Down-regulation
• excess hormone leads to a decrease in number of
  receptors
• receptors undergo endocytosis and are degraded
• decreases sensitivity of target cell to hormone
• Up-regulation
• deficiency of hormone leads to an increase in the
  number of receptors
• target tissue becomes more sensitive to the
  hormone

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Blocking Hormone Receptors

• Synthetic drugs may block receptors for naturally
  occurring hormones
• Normally, progesterone levels drop once/month
  leading to menstruation. Progesterone levels are
  maintained when a woman becomes pregnant.
• RU486 (mifepristone) binds to the receptors for
  progesterone preventing progesterone from
  sustaining the endometrium in a pregnant woman
• brings on menstrual cycle
• used to induce abortion

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Circulating and Local Hormones

• Hormones that travel in blood and act on distant
  target cells are called circulating hormones or
  endocrines.
• Hormones that act locally without first entering
  the blood stream are called local hormones.
• Those that act on neighboring cells are called
  paracrines.
• Those that act on the same cell that secreted
  them are termed autocrines.
• Figure 18.2 compares the site of action of
  circulating and local hormones.

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Circulating Local Hormones

• Circulating hormones
• Local hormones
• paracrines
• autocrines

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Chemical Classes of Hormones - Overview

• Table 18.2 provides a summary of the hormones.
• Lipid-soluble hormones include the steroids,
  thyroid hormones, and nitric oxide, which acts as
  a local hormone in several tissues.
• Water-soluble hormones include the amines
  peptides, proteins, and glycoproteins and
  eicosanoids.

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Lipid-soluble Hormones

• Steroids
• lipids derived from cholesterol on SER
• different functional groups attached to core of
  structure provide uniqueness
• Thyroid hormones
• tyrosine ring plus attached iodines are
  lipid-soluble
• Nitric oxide is gas

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Water-soluble Hormones

• Amine, peptide and protein hormones
• modified amino acids or amino acids put together
• serotonin, melatonin, histamine, epinephrine
• some glycoproteins
• Eicosanoids
• derived from arachidonic acid (fatty acid)
• prostaglandins or leukotrienes

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Hormone Transport in Blood

• Protein hormones circulate in free form in blood
• Steroid (lipid) thyroid hormones must attach to
  transport proteins synthesized by liver
• improve transport by making them water-soluble
• slow loss of hormone by filtration within kidney
• create reserve of hormone
• only 0.1 to 10 of hormone is not bound to
  transport protein free fraction

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General Mechanisms of Hormone Action

• Hormone binds to cell surface or receptor inside
  target cell
• Cell may then
• synthesize new molecules
• change permeability of membrane
• alter rates of reactions
• Each target cell responds to hormone differently
• At liver cells---insulin stimulates glycogen
  synthesis
• At adipocytes---insulin stimulates triglyceride
  synthesis

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Action of Lipid-Soluble Hormone

• Lipid-soluble hormones bind to and activate
  receptors within cells.
• The activated receptors then alter gene
  expression which results in the formation of new
  proteins.
• The new proteins alter the cells activity and
  result in the physiological responses of those
  hormones.
• Figure 18.3 shows this mechanism of action.

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Action of Lipid-Soluble Hormones

• Hormone diffuses through phospholipid bilayer
  into cell
• Binds to receptor turning on/off specific genes
• New mRNA is formed directs synthesis of new
  proteins
• New protein alters cells activity

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Action of Water-Soluble Hormones

• Water-soluble hormones alter cell functions by
  activating plasma membrane receptors, which set
  off a cascade of events inside the cell.
• The water-soluble hormone that binds to the cell
  membrane receptor is the first messenger.
• A second messenger is released inside the cell
  where hormone stimulated response takes place.
• A typical mechanism of action of a water-soluble
  hormone using cyclic AMP as the second messenger
  is seen in Figure 18.4.

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Action of Water-Soluble Hormones

• The hormone binds to the membrane receptor.
• The activated receptor activates a membrane
  G-protein which turns on adenylate cyclase.
• Adenylate cyclase converts ATP into cyclic AMP
  which activates protein kinases.
• Protein kinases phosphorylate enzymes which
  catalyze reactions that produce the physiological
  response.
• Since hormones that bond to plasma membrane
  receptors initiate a cascade of events, they can
  induce their effects at very low concentrations.

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Action of Water-Soluble Hormones

• Can not diffuse through plasma membrane
• Hormone receptors are integral membrane proteins
• act as first messenger
• The hormone binds to the membrane receptor.
• The activated receptor activates a membrane
  G-protein which turns on adenylate cyclase.
• Adenylate cyclase converts ATP into cyclic AMP
  which activates protein kinases.
• Protein kinases phosphorylate enzymes which
  catalyze reactions that produce the physiological
  response.

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Water-soluble Hormones

• Cyclic AMP is the 2nd messenger
• kinases in the cytosol speed up/slow down
  physiological responses
• Phosphodiesterase inactivates cAMP quickly
• Cell response is turned off unless new hormone
  molecules arrive

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Second Messengers

• Some hormones exert their influence by increasing
  the synthesis of cAMP
• ADH, TSH, ACTH, glucagon and epinephrine
• Some exert their influence by decreasing the
  level of cAMP
• growth hormone inhibiting hormone
• Other substances can act as 2nd messengers
• calcium ions
• cGMP
• A hormone may use different 2nd messengers in
  different target cells

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Amplification of Hormone Effects

• Single molecule of hormone binds to receptor
• Activates 100 G-proteins
• Each activates an adenylate cyclase molecule
  which then produces 1000 cAMP
• Each cAMP activates a protein kinase, which may
  act upon 1000s of substrate molecules
• One molecule of epinephrine may result in
  breakdown of millions of glycogen molecules into
  glucose molecules

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Cholera Toxin and G Proteins

• Toxin is deadly because it produces massive
  watery diarrhea and person dies from dehydration
• Toxin of cholera bacteria causes G-protein to
  lock in activated state in intestinal epithelium
• Cyclic AMP causes intestinal cells to actively
  transport chloride (Na and water follow) into
  the lumen
• Person die unless ions and fluids are replaced
  receive antibiotic treatment

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Hormonal Interactions

• The responsiveness of a target cell to a hormone
  depends on the hormones concentration, the
  abundance of the target cells hormone receptors,
  and influences exerted by other hormones.
• Three hormonal interactions are the
• permissive effect
• synergistic effect
• antagonist effect

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Hormonal Interactions

• Permissive effect
• a second hormone, strengthens the effects of the
  first
• thyroid strengthens epinephrines effect upon
  lipolysis
• Synergistic effect
• two hormones acting together for greater effect
• estrogen LH are both needed for oocyte
  production
• Antagonistic effects
• two hormones with opposite effects
• insulin promotes glycogen formation glucagon
  stimulates glycogen breakdown

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Control of Hormone Secretion

• Regulated by signals from nervous system,
  chemical changes in the blood or by other
  hormones
• Negative feedback control (most common)
• decrease/increase in blood level is reversed
• Positive feedback control
• the change produced by the hormone causes more
  hormone to be released
• Disorders involve either hyposecretion or
  hypersecretion of a hormone

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HYPOTHALAMUS AND PITUITARY GLAND

• The hypothalamus is the major integrating link
  between the nervous and endocrine systems.
• Hypothalamus receives input from cortex,
  thalamus, limbic system internal organs
• Hypothalamus controls pituitary gland with 9
  different releasing inhibiting hormones
• The hypothalamus and the pituitary gland
  (hypophysis) regulate virtually all aspects of
  growth, development, metabolism, and homeostasis.

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Anatomy of Pituitary Gland

• The pituitary gland is located in the sella
  turcica of the sphenoid bone and is
  differentiated into the anterior pituitary
  (adenohypophysis), the posterior pituitary
  (neurohypophysis), and pars intermedia (avascular
  zone in between (Figures 18.5 and 18.21b).
• Pea-shaped, 1/2 inch gland found in sella turcica
  of sphenoid
• Infundibulum attaches it to brain
• Anterior lobe 75
• develops from roof of mouth
• Posterior lobe 25
• ends of axons of 10,000 neurons found in
  hypothalamus
• neuroglial cells called pituicytes

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Anterior Pituitary Gland (Adenohypophysis)

• The blood supply to the anterior pituitary is
  from the superior hypophyseal arteries.
• Hormones of the anterior pituitary and the cells
  that produce the
• Human growth hormone (hGH) is secreted by
  somatotrophs.
• Thyroid-stimulating hormone (TSH) is secreted by
  thyrotrophs.
• Follicle-stimulating hormone (FSH) and
  luteinizing hormone (LH) are secreted by
  gonadotrophs.
• Prolactin (PRL) is secreted by lactrotrophs.
• Adrenocorticotrophic hormone (ACTH) and
  melanocyte-stimulating hormone (MSH) are secreted
  by corticotrophs.

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Flow of Blood to Anterior Pituitary

• Controlling hormones enter blood
• Travel through portal veins
• Enter anterior pituitary at capillaries

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Anterior Pituitary
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Feedback

• Secretion of anterior pituitary gland hormones is
  regulated by hypothalamic regulating hormones and
  by negative feedback mechanisms (Figure 18.6,
  Table 18.3).

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Negative Feedback Systems

• Decrease in blood levels
• Receptors in hypothalamus thyroid
• Cells activated to secrete more TSH or more T3
  T4
• Blood levels increase

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Positive Feedback

• Oxytocin stimulates uterine contractions
• Uterine contractions stimulate oxytocin release

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Human Growth Hormone and Insulin-like Growth
Factors

• Human growth hormone (hGH) is the most plentiful
  anterior pituitary hormone.
• It acts indirectly on tissues by promoting the
  synthesis and secretion of small protein hormones
  called insulin-like growth factors (IGFs).
• IGFs stimulate general body growth and regulate
  various aspects of metabolism.
• Various stimuli promote and inhibit hGH
  production (Figure 18.7).
• One symptom of excess hGH is hyperglycemia.
  (Clinical Application)

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Human Growth Hormone

• Produced by somatotrophs
• target cells synthesize insulinlike growth
• common target cells are liver, skeletal muscle,
  cartilage and bone
• increases cell growth cell division by
  increasing their uptake of amino acids
  synthesis of proteins
• stimulate lipolysis in adipose so fatty acids
  used for ATP
• retard use of glucose for ATP production so blood
  glucose levels remain high enough to supply brain

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Regulation of hGH

• Low blood sugar stimulates release of GHRH from
  hypothalamus
• anterior pituitary releases more hGH, more
  glycogen broken down into glucose by liver cells
• High blood sugar stimulates release of GHIH from
  hypothalamus
• less hGH from anterior pituitary, glycogen does
  not breakdown into glucose

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Diabetogenic Effect of Human Growth Hormone

• Excess of growth hormone
• raises blood glucose concentration
• pancreas releases insulin continually
• beta-cell burnout
• Diabetogenic effect
• causes diabetes mellitis if no insulin activity
  can occur eventually

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Thyroid Stimulating Hormone (TSH)

• Hypothalamus regulates thyrotroph cells
• Thyrotroph cells produce TSH
• TSH stimulates the synthesis secretion of T3
  and T4
• Metabolic rate stimulated

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Follicle Stimulating Hormone (FSH)

• Releasing hormone from hypothalamus
  controls
  gonadotrophs
• Gonadotrophs release
  follicle stimulating hormone
• FSH functions
• initiates the formation of follicles within the
  ovary
• stimulates follicle cells to secrete estrogen
• stimulates sperm production in testes

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Luteinizing Hormone (LH)

• Releasing hormones from hypothalamus stimulate
  gonadotrophs
• Gonadotrophs produce LH
• In females, LH stimulates
• secretion of estrogen
• ovulation of 2nd oocyte from ovary
• formation of corpus luteum
• secretion of progesterone
• In males, LH stimulates the interstitial cells of
  the testes to secrete testosterone.

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Prolactin (PRL)

• Prolactin (PRL), together with other hormones,
  initiates and maintains milk secretion by the
  mammary glands.
• Hypothalamus regulates lactotroph
  cells
• Lactotrophs produce prolactin
• Under right conditions, prolactin causes
  milk production
• Suckling reduces levels of hypothalamic
  inhibition and prolactin levels rise along with
  milk production

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Adrenocorticotrophic Hormone

• Adrenocorticotrophic hormone (ACTH) controls the
  production and secretion of hormones called
  glucocorticoids by the cortex of the adrenal
  gland.
• Hypothalamus releasing hormones stimulate
  corticotrophs
• Corticotrophs secrete ACTH MSH
• ACTH stimulates cells of the adrenal cortex that
  produce glucocorticoids

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Melanocyte-Stimulating Hormone

• Melanocyte-stimulating hormone (MSH) increases
  skin pigmentation although its exact role in
  humans is unknown.
• Releasing hormone from hypothalamus increases MSH
  release from the anterior pituitary
• Secreted by corticotroph cells
• Function not certain in humans (increase skin
  pigmentation in frogs )

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Posterior Pituitary Gland (Neurohypophysis)

• Although the posterior pituitary gland does not
  synthesize hormones, it does store and release
  two hormones.
• Hormones made by the hypothalamus and stored in
  the posterior pituitary are oxytocin (OT) and
  antidiuretic hormone (ADH).
• The neural connection between the hypothalamus
  and the neurohypophysis is via the
  hypothalamohypophyseal tract (Figure 18.8).

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Posterior Pituitary Gland (Neurohypophysis)

• Does not synthesize hormones
• Consists of axon terminals of hypothalamic
  neurons
• Neurons release two neurotransmitters into
  capillaries
• antidiuretic hormone
• oxytocin

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Oxytocin

• Two target tissues both involved in
  neuroendocrine reflexes
• During delivery
• babys head stretches cervix
• hormone release enhances uterine muscle
  contraction
• baby placenta are delivered
• After delivery
• Oxytocin stimulates contraction of the uterus and
  ejection (let-down) of milk from the breasts.
• Nursing a baby after delivery stimulates oxytocin
  release, promoting uterine contractions and the
  expulsion of the placenta (Clinical Application).
• suckling hearing babys cry stimulates milk
  ejection

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Oxytocin during Labor

• Stimulation of uterus by baby
• Hormone release from posterior pituitary
• Uterine smooth muscle contracts until birth of
  baby
• Baby pushed into cervix, increase hormone release
• More muscle contraction occurs
• When baby is born, positive feedback ceases

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ADH

• Antidiuretic hormone stimulates water
  reabsorption by the kidneys and arteriolar
  constriction.
• The effect of ADH is to decrease urine volume and
  conserve body water.
• ADH is controlled primarily by osmotic pressure
  of the blood (Figure 18.9).

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Antidiuretic Hormone (ADH)

• Known as vasopressin
• Functions
• decrease urine production
• decrease sweating
• increase BP

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Regulation of ADH

• Dehydration
• ADH released
• Overhydration
• ADH inhibited

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THYROID GLAND - Overview

• The thyroid gland is located just below the
  larynx and has right and left lateral lobes
  (Figure 18.10a).
• Histologically, the thyroid consists of the
  thyroid follicles composed of follicular cells,
  which secrete the thyroid hormones thyroxine (T4)
  and triiodothyronine (T3), and parafollicular
  cells, which secrete calcitonin (CT) (Figures
  18.10b and 18.13c).

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Thyroid Gland

• On each side of trachea is lobe of thyroid
• Weighs 1 oz has rich blood supply

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Histology of Thyroid Gland

• Follicle sac of stored hormone (colloid)
  surrounded by follicle cells that produced it
• T3 T4
• Inactive cells are short
• In between cells called parafollicular cells
• produce calcitonin

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Photomicrograph of Thyroid Gland
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Formation, Storage, and Release of Thyroid
Hormones

• Thyroid hormones are synthesized from iodine and
  tyrosine within a large glycoprotein molecule
  called thyroglobulin (TGB) and are transported in
  the blood by plasma proteins, mostly
  thyroxine-binding globulin (TBG).
• The formation, storage, and release steps include
  
• iodide trapping,
• synthesis of thyroglobulin,
• oxidation of iodide,
• iodination of tyrosine,
• coupling of T1 and T2,
• pinocytosis and digestion of colloid,
• secretion of thyroid hormones, and transport in
  blood (Figure 18.11).

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Formation of Thyroid Hormone

• Iodide trapping by follicular cells
• Synthesis of thyroglobulin (TGB)
• Release of TGB into colloid
• Iodination of tyrosine in colloid
• Formation of T3 T4 by combining T1 and T2
  together
• Uptake digestion of TGB by follicle cells
• Secretion of T3 T4 into blood

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Actions of Hormones from Thyroid Gland

• T3 T4
• thyroid hormones responsible for our metabolic
  rate, synthesis of protein, breakdown of fats,
  use of glucose for ATP production
• Calcitonin
• responsible for building of bone stops
  reabsorption of bone (lowers blood levels of
  Calcium)

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Control of T3 T4 Secretion

• Negative feedback system
• Low blood levels of hormones stimulate
  hypothalamus
• It stimulates pituitary to release TSH
• TSH stimulates gland to raise blood levels

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PARATHYROID GLANDS

• The parathyroid glands are embedded on the
  posterior surfaces of the lateral lobes of the
  thyroid
• principal cells produce parathyroid hormone
• oxyphil cells function is unknown (Figure
  18.13).
• Parathyroid hormone (PTH) regulates the
  homeostasis of calcium and phosphate
• increase blood calcium level
• decrease blood phosphate level
• increases the number and activity of osteoclasts
• increases the rate of Ca2 and Mg2 from
  reabsorption from urine and inhibits the
  reabsorption of HPO4-2 so more is secreted in the
  urine
• promotes formation of calcitriol, which increases
  the absorption of Ca2, Mg2,and HPO4-2 from the
  GI tract

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Parathyroid Glands

• 4 pea-sized glands found on back of thyroid gland

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Histology of Parathyroid Gland

• Principal cells produce parathyroid hormone (PTH)
• Oxyphil cell function is unknown

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Blood Calcium

• Blood calcium level directly controls the
  secretion of calcitonin and parathyroid hormone
  via negative feedback loops that do not involve
  the pituitary gland (Figure 18.14).
• Table 18.7 summarizes the principal actions and
  control of secretion of parathyroid hormone.

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Regulation of Calcium Blood Levels

• High or low blood levels of Ca2 stimulate the
  release of different hormones --- PTH or CT

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Adrenal Glands

• The adrenal glands are located superior to the
  kidneys (Figure 18.15)
• 3 x 3 x 1 cm in size and weighs 5 grams
• consists of an outer cortex and an inner medulla.
• Cortex produces 3 different types of hormones
  from 3 zones of cortex
• Medulla produces epinephrine norepinephrine

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Adrenal Cortex

• The adrenal cortex is divided into three zones,
  each of which secretes different hormones (Figure
  18.15).
• The zona glomerulosa (outer zone)
• secretes mineralocorticoids.
• The zona fasciculata (middle zone)
• secretes glucocorticoids.
• The zona reticularis (inner zone)
• secretes androgens.

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Histology of AdrenalGland

• Cortex
• 3 zones
• Medulla

70
Structure of Adrenal Gland

• Cortex derived from mesoderm
• Medulla derived from ectoderm

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Mineralocorticoids

• 95 of hormonal activity due to aldosterone
• Functions
• increase reabsorption of Na with Cl- ,
  bicarbonate and water following it
• promotes excretion of K and H
• Hypersecretion tumor producing aldosteronism
• high blood pressure caused by retention of Na
  and water in blood

72
Regulation of Aldosterone
73
Glucocorticoids

• 95 of hormonal activity is due to cortisol
• Functions help regulate metabolism
• increase rate of protein catabolism lipolysis
• conversion of amino acids to glucose
• stimulate lipolysis
• provide resistance to stress by making nutrients
  available for ATP production
• raise BP by vasoconstriction
• anti-inflammatory effects reduced (skin cream)
• reduce release of histamine from mast cells
• decrease capillary permeability
• depress phagocytosis

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Regulation of Glucocorticoids

• Negative feedback

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Androgens from Zona Reticularis

• Small amount of male hormone produced
• insignificant in males
• may contribute to sex drive in females
• is converted to estrogen in postmenopausal females

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Adrenal Medulla

• Chromaffin cells receive direct innervation from
  sympathetic nervous system
• develop from same tissue as postganglionic
  neurons
• Produce epinephrine norepinephrine
• Hormones are sympathomimetic
• effects mimic those of sympathetic NS
• cause fight-flight behavior
• Acetylcholine increase hormone secretion by
  adrenal medulla

77
PANCREATIC ISLETS

• The pancreas is a flattened organ located
  posterior and slightly inferior to the stomach
  and can be classified as both an endocrine and an
  exocrine gland (Figure 18.18).
• Histologically, it consists of pancreatic islets
  or islets of Langerhans (Figure 18.19) and
  clusters of cells (acini) (enzyme-producing
  exocrine cells).

78
Anatomy of Pancreas

• Organ (5 inches) consists of head, body tail
• Cells (99) in acini produce digestive enzymes
• Endocrine cells in pancreatic islets produce
  hormones

79
Cell Organization in Pancreas

• Exocrine acinar cells surround a small duct
• Endocrine cells secrete near a capillary

80
Histology of the Pancreas

• 1 to 2 million pancreatic islets
• Contains 4 types of endocrine cells

81
Cell Types in the Pancreatic Islets

• Alpha cells (20) produce glucagon
• Beta cells (70) produce insulin
• Delta cells (5) produce somatostatin
• F cells produce pancreatic polypeptide

82
Regulation

• Regulation of glucagon and insulin secretion is
  via negative feedback mechanisms (Figure 18.19).
• Low blood glucose stimulates release of glucagon
• High blood glucose stimulates secretion of
  insulin
• Table 18.9 summarizes the hormones produced by
  the pancreas, their principal actions, and
  control of secretion.

83
Ovaries and Testes

• Ovaries
• estrogen, progesterone, relaxin inhibin
• regulate reproductive cycle, maintain pregnancy
  prepare mammary glands for lactation
• Testes
• produce testosterone
• regulate sperm production 2nd sexual
  characteristics
• Table 18.10 summarizes the hormones produced by
  the ovaries and testes and their principal
  actions.

84
Pineal Gland

• Small gland attached to 3rd ventricle of brain
• Consists of pinealocytes neuroglia
• Melatonin responsible for setting of biological
  clock
• Jet lag SAD treatment is bright light

85
Effect of Light on Pineal Gland

• Melatonin secretion producing sleepiness occurs
  during darkness due to lack of stimulation from
  sympathetic ganglion

86
Seasonal Affective Disorder and Jet Lag

• Depression that occurs during winter months when
  day length is short
• Due to overproduction of melatonin
• Therapy
• exposure to several hours per day of artificial
  light as bright as sunlight
• speeds recovery from jet lag

87
Thymus Gland

• Important role in maturation of T cells
• Hormones produced by gland promote the
  proliferation maturation of T cells
• thymosin
• thymic humoral factor
• thymic factor
• thymopoietin

88
OTHER HORMONES and GROWTH FACTORS

• Several body tissues other than those usually
  classified as endocrine glands also contain
  endocrine tissue and thus secrete hormones.
• Table 18.11 summarizes these hormones and their
  actions.

89
Eicosanoids

• Local hormones released by all body cells
• alter the production of second messengers, such
  as cyclic AMP
• Leukotrienes influence WBCs inflammation
• Prostaglandins alter
• smooth muscle contraction, glandular secretion,
  blood flow, platelet function, nerve
  transmission, metabolism.
• Aspirin and related nonsteroidal
  anti-inflammatory drugs (NSAIDS), such as
  ibuprofen and acetaminophen, inhibit a key enzyme
  in prostaglandin synthesis and are used to treat
  a wide variety of inflammatory disorders.

90
Nonsteroidal Anti-inflammatory Drugs

• Answer to how aspirin or ibuprofen works was
  discovered in 1971
• inhibit a key enzyme in prostaglandin synthesis
  without affecting the synthesis of leukotrienes
• Treat a variety of inflammatory disorders
• rheumatoid arthritis
• Usefulness of aspirin to treat fever pain
  implies prostaglandins are responsible for those
  symptoms

91
Growth Factors

• Substances with mitogenic qualities
• cause cell growth from cell division
• Many act locally as autocrines or paracrines
• Selected list of growth factors (Table 18.12)
• epidermal growth factor (EGF),
• platelet-derived growth factor (PDGF),
• fibroblast growth factor (FGF),
• nerve growth factor (NGF),
• tumor angiogenesis factors (TAFs),
• Insulin-like growth factor (IFG),
• cytokines

92
STRESS RESPONSE

• The stimuli that produce the general adaptation
  syndrome are called stressors.
• Stressors include almost any disturbance heat or
  cold, surgical operations, poisons, infections,
  fever, and strong emotional responses.
• Stages of the General Adaptation Syndrome

93
Stress General Adaptation Syndrome

• Stress response is set of bodily changes called
  general adaptation syndrome (GAS)
• Any stimulus that produces a stress response is
  called a stressor
• Stress resets the body to meet an emergency
• eustress is productive stress helps us prepare
  for certain challenges
• distress type levels of stress are harmful
• lower our resistance to infection

94
General Adaptation Syndrome
95
Alarm Reaction (Fight-or-Flight)

• The alarm reaction is initiated by nerve impulses
  from the hypothalamus to the sympathetic division
  of the autonomic nervous system and adrenal
  medulla (Figure 18.20a).
• Dog attack
• increases circulation
• promote catabolism for energy production
• promotes ATP synthesis
• nonessential body functions are inhibited
• digestive, urinary reproductive

96
Resistance Reaction

• Initiated by hypothalamic releasing hormones
  (long-term reaction to stress)
• corticotropin, growth hormone thyrotropin
  releasing hormones
• Results
• increased secretion of aldosterone acts to
  conserve Na (increases blood pressure) and
  eliminate H
• increased secretion of cortisol so protein
  catabolism is increased other sources of
  glucose are found
• increase thyroid hormone to increase metabolism
• Allow body to continue to fight a stressor
• Glucocorticoids are produced in high
  concentrations during stress. They create many
  distinct physiological effects.

97
Exhaustion

• Exhaustion is caused mainly by loss of potassium,
  depletion of adrenal glucocorticoids, and
  weakened organs. If stress is too great, it may
  lead to death.
• Resources of the body have become depleted
• Resistance stage can not be maintained
• Prolonged exposure to resistance reaction
  hormones
• wasting of muscle
• suppression of immune system
• ulceration of the GI tract
• failure of the pancreatic beta cells

98
Stress and Disease

• Stress can lead to disease by inhibiting the
  immune system
• gastritis, ulcerative colitis, irritable bowel
  syndrome, peptic ulcers, hypertension, asthma,
  rheumatoid arthritis, migraine headaches,
  anxiety, and depression.
• people under stress are at a greater risk of
  developing chronic disease or of dying
  prematurely
• Interleukin - 1
• link between stress and immunity
• secreted by macrophages stimulates secretion of
  ACTH
• stimulates production of immune substances
• feedback control since immune substance suppress
  the formation of interleukin-1

99
DEVELOPMENTAL ANATOMY OF THE ENDOCRINE SYSTEM

• The pituitary gland originates from two different
  regions of the ectoderm.
• The anterior pituitary derives from the
  neurohypophyseal bud, located on the floor of the
  hypothalamus (Figure 18.21).
• The anterior pituitary is derived from an
  outgrowth of ectoderm from the mouth called the
  hypophyseal (Rathkes) pouch.
• The thyroid gland develops as a midventral
  outgrowth of endoderm, called the thyroid
  diverticulum, from the floor of the pharynx at
  the level of the second pair of pharyngeal
  pouches.
• Parathyroid glands develop from endoderm as
  outgrowths from the third and fourth pharyngeal
  pouches.

100
Development of the Endocrine System

• Thyroid develops ---floor of pharynx 2nd pouch
• Parathyroid thymus --3 4 pharyngeal pouches
• Pancreas from foregut

101
Development of Pituitary Gland

• Events occurring between 5 and 16 weeks of age

102
DEVELOPMENTAL ANATOMY OF THE ENDOCRINE SYSTEM

• The adrenal cortex is derived from intermediate
  mesoderm from the same region that produces the
  gonads. The adrenal medulla is ectodermal in
  origin and derives from the neural crest, which
  also gives rise to sympathetic ganglion and other
  nervous system structures (Figure 14.125b).
• The pancreas develops from the outgrowth of
  endoderm from the part of the foregut that later
  becomes the duodenum (Figure 29.12c).
• The pineal gland arises as an outgrowth between
  the thalamus and colliculi from ectoderm
  associated with the diencephalon (Figure 14.26).
• The thymus gland arises from endoderm of the
  third pharyngeal pouch.

103
Aging and the Endocrine System

• Production of human growth hormone decreases
• muscle atrophy
• Production of TSH increase with age to try and
  stimulate thyroid
• decrease in metabolic rate, increase in body fat
  hypothyroidism
• Thymus after puberty is replaced with adipose
• Adrenal glands produce less cortisol
  aldosterone
• Receptor sensitivity to glucose declines
• Ovaries no longer respond to gonadotropins
• decreased output of estrogen (osteoporosis
  atherosclerosis)

104
DISORDERS HOMEOSTATIC IMBALANCES
105
Diabetes Insipidus

• dysfunction of the posterior pituitary
• Hyposecretion of ADH
• excretion of large amounts of dilute urine and
  subsequent dehydration and thirst

106
Pituitary Gland Disorders

• Hyposecretion during childhood pituitary
  dwarfism (proportional, childlike body)
• Hypersecretion during childhood giantism
• very tall, normal proportions
• Hypersecretion as adult acromegaly
• growth of hands, feet, facial features
  thickening of skin

107
Thyroid Gland Disorders

• Hyposecretion during infancy results in dwarfism
  retardation called cretinism
• Hypothyroidism in adult produces sensitivity to
  cold, low body temp. weight gain mental
  dullness
• Hyperthyroidism (Graves disease)
• weight loss, nervousness, tremor exophthalmos
  (edema behind eyes)
• Goiter enlarged thyroid (dietary)

108
Parathyroid Gland Disorders

• Hypoparathyroidism results in muscle tetany.
• Hyperparathyroidism produces osteitis fibrosa
  cystica

109
Adrenal Gland Disorders - Tumor

• Pheochromocytomas, benign tumors of the adrenal
  medulla, cause hypersecretion of medullary
  hormones and a prolonged fight-or-flight response.

110
Adrenal Gland Disorders - Cushings Syndrome

• Hypersecretion of glucocorticoids
• Redistribution of fat, spindly arms legs due to
  muscle loss
• Wound healing is poor, bruise easily

111
Adrenal Gland Disorders - Addisons disease

• Hypersecretion of glucocorticoids
• hypoglycemia, muscle weakness, low BP,
  dehydration due to decreased Na in blood
• mimics skin darkening effects of MSH
• potential cardiac arrest

112
Pancreatic Disorders

• Diabetes Mellitus
• This is a group of disorders caused by an
  inability to produce or use insulin.
• Type I diabetes or insulin-dependent diabetes
  mellitus is caused by an absolute deficiency of
  insulin.
• Type II diabetes or insulin-independent diabetes
  is caused by a down-regulation of insulin
  receptors.
• excessive urine production (polyuria)
• excessive thirst (polydipsia)
• excessive eating (polyphagia)
• Hyperinsulinism results when too much insulin is
  present
• causes hypoglycemia and possibly insulin shock

113

• end

114
Photographs for Review

• Figure 18.22 shows photographs of individuals
  suffering from various endocrine disorders.

115
Adrenal Cortex - Review

• Mineralocorticoids
• Mineralocorticoids (e.g., aldosterone) increase
  sodium and water reabsorption and decrease
  potassium reabsorption, helping to regulate
  sodium and potassium levels in the body.
• Secretion is controlled by the renin-angiotensin
  pathway (Figure 18.16) and the blood level of
  potassium.
• Glucocorticoids
• Glucocorticoids (e.g., cortisol) promote
  breakdown of proteins, formation of glucose,
  lipolysis, resistance to stress,
  anti-inflammatory effects, and depression of the
  immune response.
• Secretion is controlled by CRH (corticotropin
  releasing hormone) and ACTH (adrenocorticotropic
  hormone) from the anterior pituitary (Figure
  18.17).
• Androgens
• Androgens secreted by the adrenal cortex usually
  have minimal effects.

116
Adrenal Medulla - Review

• The adrenal medulla consists of hormone-producing
  cells, called chromaffin cells, which surround
  large blood-filled sinuses.
• Medullary secretions are epinephrine and
  norepinephrine (NE), which produce effects
  similar to sympathetic responses.
• They are released under stress by direct
  innervation from the autonomic nervous system.
  Like the glucocorticoids of the adrenal cortex,
  these hormones help the body resist stress.
  However, unlike the cortical hormones, the
  medullary hormones are not essential for life.
• Table 18.8 summarizes the hormones produced by
  the adrenal glands, the principal actions, and
  control of secretion.

117
Review Cell Types in the Pancreatic Islets

• Alpha cells secrete the hormone glucagon which
  increases blood glucose levels.
• Beta cells secrete the hormone insulin which
  decreases blood glucose levels.
• Delta cells secrete growth hormone inhibiting
  hormone or somatostatin, which acts as a
  paracrine to inhibit the secretion of insulin and
  glucagon.
• F-cells secrete pancreatic polypeptide, which
  regulates release of pancreatic digestive enzymes.

118
OVARIES AND TESTES - Review

• Ovaries are located in the pelvic cavity and
  produce sex hormones (estrogens and progesterone)
  related to development and maintenance of female
  sexual characteristics, reproductive cycle,
  pregnancy, lactation, and normal reproductive
  functions. The ovaries also produce inhibin and
  relaxin.
• Testes lie inside the scrotum and produce sex
  hormones (primarily testosterone) related to the
  development and maintenance of male sexual
  characteristics and normal reproductive
  functions. The testes also produce inhibin.

119
PINEAL GLAND - Review

• The pineal gland (epiphysis cerebri) is attached
  to the roof of the third ventricle, inside the
  brain (Figure 18.1).
• Histologically, it consists of secretory
  parenchymal cells called pinealocytes, neuroglia
  cells, and scattered postganglionic sympathetic
  fibers. The pineal secrets melatonin in a diurnal
  rhythm linked to the dark-light cycle.
• Seasonal affective disorder (SAD), a type of
  depression that arises during the winter months
  when day length is short, is thought to be due,
  in part, to over-production of melatonin. Bright
  light therapy, repeated doses of several hours
  exposure to artificial light as bright as
  sunlight, may provide relief for this disorder
  and for jet lag.

120
THYMUS GLAND

• The thymus gland secretes several hormones
  related to immunity .
• Thymosin, thymic humoral-factor, thymic factor,
  and thymopoietin promote the proliferation and
  maturation of T cells, a type of white blood cell
  involved in immunity.