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Endocrine Physiology and
Mechanisms of Hypothalamic-
    Pituitary Regulation

         Chapter 39
Endocrine System

 • Composed of cells and organs that are specialized to
   synthesize and secrete hormones into the
   bloodstream to act at distant target cells

 • Hormones are blood-borne chemical messengers
   that affect target cells anatomically distant from the
   secreting cell
How to go through the Endocrine
                 System?

•   What is the gland?
•   What triggers it to secrete?
•   What is the secreted product (hormone)?
•   What is the target of the hormone?
•   What is the resulting work of the hormone?
THEN…..
• Three things that make a gland secrete:

1. Hormonal stimulation
   – Hormone to hormone
      • Hypothalamus  pituitary
      • Pituitary  thymus
2. Humoral fluids
   – What ions/proteins in the fluids
      • Ca2+ levels, blood sugar
3. The Nervous System
   – Sympathetic stimuli
      • Epinephrine and norepinephrine
Endocrine vs. Exocrine Glands

  Where do they secrete their products?
Endocrine System
HORMONAL CONTROL
What is negative feedback?
• Occurs when there is a
  drop in the level of a
  hormone
 – triggers a chain reaction of
   responses to increase
   hormones in the blood
 – most hormones are
   regulated by negative
   feedback
 – OXYTOCIN: POSITIVE
   FEEDBACK
Where is the hormone going?
• Only the target cells for a given hormone
  have receptors that bind and recognize that
  hormone.
Endocrine Glands
Endocrine Glands
Endocrine Glands
Hormones

• Neurocrine—secretion of
  hormones into the bloodstream
  by neurons
• Endocrine—secretion of
  hormones into the bloodstream
  by endocrine glands
• Paracrine—hormone molecule
  secreted by one cell affects
  adjacent cells
• Autocrine—hormone molecule
  secreted by a cell affects the
  secreting cell
Hormones

 • Water soluble
   – Peptides
   – Tyrosine-derived catecholamines:
      • Epinephrine, Norepinephrine, Dopamine

 • Lipid soluble
    – Tyrosine-derived Thyroid hormones:
      • T3, T4
   – Steroids
Hormones: Tyrosine-derived catecholamines
Hormones: Tyrosine-derived thyroid hormones
Hormones:   steroids
Hormones: Mechanism of action

  Hormones with Cell Membrane Receptors
  • Water-soluble hormones have a hormone-binding site located
    on the external portion of a specific cell-surface receptor
  • Hormones exert their action by binding to target cell receptor
    proteins
  • Once binding takes place, a conformation of the receptor
    protein conveys a signal to the interior of the cell
  • Amplification of the hormone activity is achieved by activation
    of a cascade of chemical reactions
Hormones: Mechanism of action
      Hormones with Cell Membrane Receptors




               Water Soluble Hormones
Hormones: Mechanism of action
     Hormones with Cell Membrane Receptors
Hormones: Mechanism of action

  Hormones with Intracellular Receptors
  • Lipid-soluble (thyroid and steroid) hormones diffuse easily through
    the lipid bilayer of cell membranes
  • Receptors for these hormones are located in the cytoplasm, or in
    the nucleus of the target cell
  • Binding causes a change in affinity of the receptor for binding sites
    on DNA in the cell nucleus
  • Gene expression is changed by binding of the hormone-receptor
    complex to specific DNA binding sites
  • Onset of action of lipid-soluble hormones is slow compared with
    water-soluble hormones and there is no amplification cascade
Lipid-Soluble Hormones
Hormones: Regulation
    Hormone Synthesis, Secretion, Metabolism
    • Most endocrine hormones are polypeptides
      manufactured on the rough endoplasmic reticulum and
      stored in vesicles within the cells
    • Cleaved by specific enzymes to release the active form
      of the hormone


                             Enzyme

           Pre hormone                   Cleavage   Hormone
                                         fragment
Hormones: Regulation


    Hormone Synthesis, Secretion, Metabolism
    • Water-soluble hormones
       – Peptide hormones: CONTAINED WITHIN LIPID BILAYER
         OF THE VESICLES and stored until a trigger results in
         exocytosis of the hormone into the extracellular space
       – Catecholamines: formed by enzymes within the cytoplasm that
         begin with tyrosine and through a series of steps convert it to
         dopamine, norepinephrine, or epinephrine
Hormones: Regulation


    Hormone Synthesis, Secretion, Metabolism
    • Lipid-soluble hormones
       – Steroid hormones: FORMED ON DEMAND from cholesterol
         that is stored in the cell or retrieved from the circulating
         lipoproteins
       – Thyroid hormones: synthesis precedes secretion by weeks or
         months in the thyroid follicle and bound to protein
         thyroglobulin; secretion occurs via cleavage of the thyroid
         hormone based on systemic needs determined by the
         hypothalamus and pituitary gland
Pituitary Gland
Pituitary Gland
Pituitary Gland

  Pituitary Gland (Hypophysis)

  • Located beneath the
    hypothalamus in the sella
    turcica

  • Connected to hypothalamus by
    the pituitary stalk
  •
  • Composed of anterior
    (adenohypophysis) and
    posterior (neurohypophysis)
    lobes
HORMONES OF THE PITUITARY
        GLAND
• Divided into two lobes
 – anterior pituitary lobe is larger and
   produces SIX hormones; stimulated by
   releasing and inhibiting hormones from the
   hypothalamus; connected by hypophyseal
   portal veins
 – posterior pituitary lobe is smaller and
   consists primarily of axons whose cell
   bodies are in the hypothalamus
Sphenoid bone
                      Portal veins deliver releasing & inhibiting hormones from hypothalamus.
    Pituitary Gland
Flow of
                                               Blood to
                                               Anterior
                                               Pituitary




•   Releasing & inhibiting hormones enter blood (hypothalamus)
•   Travel through portal veins
•   Enter anterior pituitary at capillaries
•   Hormones travel to destination
Hypothalamic Neurosecretory Cells




•Does not synthesize hormones
• Hormones packaged & travel by axons of hypothalamic neurons
Anterior vs. Posterior Lobes

•Growth Hormone         Oxytocin
(hGH)                   Antidiuretic hormone
•Thyroid Stimulating      (ADH)
hormone (TSH)
•Follicle Stimulating
Hormone (FSH)
•Luteinizing hormone
(LH)
•Prolactin (PRL)
•Adrenocorticotropic
hormone (ACTH)
Anterior Pituitary
Gland Hormones
Pituitary Gland

  • The hypothalamus regulates endocrine function of the
    ANTERIOR PITUITARY by SECRETING RELEASING AND
    INHIBITING HORMONES INTO THE PORTAL SYSTEM between
    the hypothalamus and pituitary that transports capillary blood
    from the hypothalamus to the capillaries of the anterior lobe

  • Release of POSTERIOR PITUITARY hormones occurs WHEN
    ACTION POTENTIALS GENERATED IN THE HYPOTHALAMIC
    NEURONS TRAVEL DOWN THE AXONS of the pituitary stalk
    and trigger exocytosis of hormone from the nerve terminals in
    the posterior pituitary gland
Pituitary Gland
Endocrine Glands
Posterior Pituitary   Gland
Posterior Pituitary Gland
 Target: V2 receptors
 of distal renal tubule
          cells


   Aquaporins move
  from cytoplasm to
     apical tubular
    epithelial cells
                            H20


  Water moves from
    tubular fluid


          Cell

     Interstitium
What is diabetes insipidus?

           -DECREASED ADH
           -Excretion of large amounts of
           dilute urine
           -Destruction of back of pituitary
           -OR insensitivity of kidneys to
           hormone
Endocrine Glands
Anterior Pituitary   Gland


                             Hypothalamic neurons
Anterior Pituitary Gland
Hypothalamic
hormones bind to
receptors on
pituitary cells
Thyroid Gland
On each side of trachea is lobe of thyroid




                Butterfly-shaped gland; located in the anterior
Thyroid Gland   part of neck
Thyroid Gland
 • Main function of thyroid is production and secretion of
   metabolically active hormones that are essential for regulation of
   various metabolic processes.

 • Thyroid hormones are made from tyrosine and iodine.
THYROID

– Secretes 3 hormones:
 • Thyroxine/ Tetraiodothyronine (T4)
 • Triiodthyronine (T3)
 • Calcitonin: Decreases the level of calcium
   in the blood & increases uptake of calcium
   into bone matrix
Thyroid Gland




  Most important thyroid hormones are:
   - Thyroxin (T4)
   - Triiodothyronine (T3)

   → Approximately 90% of the thyroid hormone is in the
  form of T4, whereas 10% is T3       Source: Clinical Chemistry. 2010. Kaplan and Pesce. Mosby.
Thyroid
•Follicle = sac of stored hormone



                            Makes thyroglobulin



Contains thyroglobulin
with attached iodine
molecules
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 by
   osteolasts (lowers blood
   levels of Calcium)
Thyroid Gland


Trap dietary iodine   TSH stimulation


Synthesize
thyroglobulin +
thyroid peroxidase
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
Parathyroid




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

• PTH: increases serum calcium and decreases
  serum phosphate
• PTH=Phosphate Trashing Hormone
     • 1. Increase bone reabsorption of calcium
     • 2. Increase kidney reabsorption of calcium
     • 3. Decrease kidney reabsorption of
       phosphate
     • 4. Increase Vitamin D production by
       stimulating kidney (thus, indirect increase in
       intestinal calcium)
Parathyroid
hormone (PTH)
       &
Calcitonin (CT)
Adrenal Gland
ADRENAL GLANDS
• Two adrenal glands located on top of each
  kidney; each has two parts
  – Cortex
    • Mineralocorticoids
    • Glucocorticoids        Regulation the three S’s
                             Salt, sugar and sex
    • Androgens

  – Medulla
    • epinephrine
    • norepinephrine
Adrenal Gland
Adrenal Glands
Adrenal Gland
Low
blood
flow
Adrenal Gland:   Aldosterone
Glucocorticoid: Cortisol
• Glucose formation: gluconeogenesis (prime effect)
• Breakdown of protein
    • (increase release of amino acids into blood stream)
• Breakdown of fat (lipolysis)
• Depression of Immune function
    • (Prescribed for organ transplants)
• Anti-Inflammatory effects
    • (inhibit WBC’s but also retard tissue repair)
• Resistance to stress: Provide tissues with a ready supply of ATP
Adrenal Gland:   Cortisol

                        Normally cortisol is present in the
                        body at higher levels in the morning,
                        and at its lowest at night.
Adrenal Gland:   Cortisol
Categories of Endocrine Disease

• Hyposecretion
• Hypersecretion
• Target cell hyporesponsiveness
Categories of Endocrine Disease

• Hyposecretion
  – Primary hyposecretion occurs when an
    ENDOCRINE GLAND releases an inadequate
    amount of hormone to meet physiologic needs
  – Secondary hyposecretion occurs when secretion
    of a TROPIC HORMONE is inadequate to cause the
    target gland to secrete adequate amounts of
    hormone
Categories of Endocrine Disease (Cont.)

• Hypersecretion
  – Primary hypersecretion occurs when there is a
    DYSFUNCTION OF THE ENDOCRINE GLAND that
    results in abnormally high secretion of hormone
  – Secondary hypersecretion occurs when there is an
    ELEVATION IN THE TROPIC LEVEL of one hormone
    that results in an increased plasma concentration
    of the endocrine gland hormone also
Categories of Endocrine Disease

• Target cell hyporesponsiveness
  – Typically due to lack of or a deficiency in cellular
    receptors, but can occur with postreceptor
    mechanisms, such as second-messenger
    dysfunction that causes decreased cellular
    response
  – Hormone resistance of the target tissues will
    cause the same set of clinical symptoms as
    hyposecretion

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Hypothalamic Regulation of Endocrine Glands

  • 1. Endocrine Physiology and Mechanisms of Hypothalamic- Pituitary Regulation Chapter 39
  • 2. Endocrine System • Composed of cells and organs that are specialized to synthesize and secrete hormones into the bloodstream to act at distant target cells • Hormones are blood-borne chemical messengers that affect target cells anatomically distant from the secreting cell
  • 3. How to go through the Endocrine System? • What is the gland? • What triggers it to secrete? • What is the secreted product (hormone)? • What is the target of the hormone? • What is the resulting work of the hormone?
  • 4. THEN….. • Three things that make a gland secrete: 1. Hormonal stimulation – Hormone to hormone • Hypothalamus  pituitary • Pituitary  thymus 2. Humoral fluids – What ions/proteins in the fluids • Ca2+ levels, blood sugar 3. The Nervous System – Sympathetic stimuli • Epinephrine and norepinephrine
  • 5. Endocrine vs. Exocrine Glands Where do they secrete their products?
  • 7. HORMONAL CONTROL What is negative feedback? • Occurs when there is a drop in the level of a hormone – triggers a chain reaction of responses to increase hormones in the blood – most hormones are regulated by negative feedback – OXYTOCIN: POSITIVE FEEDBACK
  • 8. Where is the hormone going? • Only the target cells for a given hormone have receptors that bind and recognize that hormone.
  • 11. Hormones • Neurocrine—secretion of hormones into the bloodstream by neurons • Endocrine—secretion of hormones into the bloodstream by endocrine glands • Paracrine—hormone molecule secreted by one cell affects adjacent cells • Autocrine—hormone molecule secreted by a cell affects the secreting cell
  • 12. Hormones • Water soluble – Peptides – Tyrosine-derived catecholamines: • Epinephrine, Norepinephrine, Dopamine • Lipid soluble – Tyrosine-derived Thyroid hormones: • T3, T4 – Steroids
  • 15. Hormones: steroids
  • 16. Hormones: Mechanism of action Hormones with Cell Membrane Receptors • Water-soluble hormones have a hormone-binding site located on the external portion of a specific cell-surface receptor • Hormones exert their action by binding to target cell receptor proteins • Once binding takes place, a conformation of the receptor protein conveys a signal to the interior of the cell • Amplification of the hormone activity is achieved by activation of a cascade of chemical reactions
  • 17. Hormones: Mechanism of action Hormones with Cell Membrane Receptors Water Soluble Hormones
  • 18. Hormones: Mechanism of action Hormones with Cell Membrane Receptors
  • 19. Hormones: Mechanism of action Hormones with Intracellular Receptors • Lipid-soluble (thyroid and steroid) hormones diffuse easily through the lipid bilayer of cell membranes • Receptors for these hormones are located in the cytoplasm, or in the nucleus of the target cell • Binding causes a change in affinity of the receptor for binding sites on DNA in the cell nucleus • Gene expression is changed by binding of the hormone-receptor complex to specific DNA binding sites • Onset of action of lipid-soluble hormones is slow compared with water-soluble hormones and there is no amplification cascade
  • 21. Hormones: Regulation Hormone Synthesis, Secretion, Metabolism • Most endocrine hormones are polypeptides manufactured on the rough endoplasmic reticulum and stored in vesicles within the cells • Cleaved by specific enzymes to release the active form of the hormone Enzyme Pre hormone Cleavage Hormone fragment
  • 22. Hormones: Regulation Hormone Synthesis, Secretion, Metabolism • Water-soluble hormones – Peptide hormones: CONTAINED WITHIN LIPID BILAYER OF THE VESICLES and stored until a trigger results in exocytosis of the hormone into the extracellular space – Catecholamines: formed by enzymes within the cytoplasm that begin with tyrosine and through a series of steps convert it to dopamine, norepinephrine, or epinephrine
  • 23. Hormones: Regulation Hormone Synthesis, Secretion, Metabolism • Lipid-soluble hormones – Steroid hormones: FORMED ON DEMAND from cholesterol that is stored in the cell or retrieved from the circulating lipoproteins – Thyroid hormones: synthesis precedes secretion by weeks or months in the thyroid follicle and bound to protein thyroglobulin; secretion occurs via cleavage of the thyroid hormone based on systemic needs determined by the hypothalamus and pituitary gland
  • 26. Pituitary Gland Pituitary Gland (Hypophysis) • Located beneath the hypothalamus in the sella turcica • Connected to hypothalamus by the pituitary stalk • • Composed of anterior (adenohypophysis) and posterior (neurohypophysis) lobes
  • 27. HORMONES OF THE PITUITARY GLAND • Divided into two lobes – anterior pituitary lobe is larger and produces SIX hormones; stimulated by releasing and inhibiting hormones from the hypothalamus; connected by hypophyseal portal veins – posterior pituitary lobe is smaller and consists primarily of axons whose cell bodies are in the hypothalamus
  • 28. Sphenoid bone Portal veins deliver releasing & inhibiting hormones from hypothalamus. Pituitary Gland
  • 29. Flow of Blood to Anterior Pituitary • Releasing & inhibiting hormones enter blood (hypothalamus) • Travel through portal veins • Enter anterior pituitary at capillaries • Hormones travel to destination
  • 30. Hypothalamic Neurosecretory Cells •Does not synthesize hormones • Hormones packaged & travel by axons of hypothalamic neurons
  • 31. Anterior vs. Posterior Lobes •Growth Hormone Oxytocin (hGH) Antidiuretic hormone •Thyroid Stimulating (ADH) hormone (TSH) •Follicle Stimulating Hormone (FSH) •Luteinizing hormone (LH) •Prolactin (PRL) •Adrenocorticotropic hormone (ACTH)
  • 32.
  • 34. Pituitary Gland • The hypothalamus regulates endocrine function of the ANTERIOR PITUITARY by SECRETING RELEASING AND INHIBITING HORMONES INTO THE PORTAL SYSTEM between the hypothalamus and pituitary that transports capillary blood from the hypothalamus to the capillaries of the anterior lobe • Release of POSTERIOR PITUITARY hormones occurs WHEN ACTION POTENTIALS GENERATED IN THE HYPOTHALAMIC NEURONS TRAVEL DOWN THE AXONS of the pituitary stalk and trigger exocytosis of hormone from the nerve terminals in the posterior pituitary gland
  • 37. Posterior Pituitary Gland Target: V2 receptors of distal renal tubule cells Aquaporins move from cytoplasm to apical tubular epithelial cells H20 Water moves from tubular fluid Cell Interstitium
  • 38. What is diabetes insipidus? -DECREASED ADH -Excretion of large amounts of dilute urine -Destruction of back of pituitary -OR insensitivity of kidneys to hormone
  • 39. Endocrine Glands Anterior Pituitary Gland Hypothalamic neurons
  • 40. Anterior Pituitary Gland Hypothalamic hormones bind to receptors on pituitary cells
  • 42. On each side of trachea is lobe of thyroid Butterfly-shaped gland; located in the anterior Thyroid Gland part of neck
  • 43. Thyroid Gland • Main function of thyroid is production and secretion of metabolically active hormones that are essential for regulation of various metabolic processes. • Thyroid hormones are made from tyrosine and iodine.
  • 44. THYROID – Secretes 3 hormones: • Thyroxine/ Tetraiodothyronine (T4) • Triiodthyronine (T3) • Calcitonin: Decreases the level of calcium in the blood & increases uptake of calcium into bone matrix
  • 45. Thyroid Gland Most important thyroid hormones are: - Thyroxin (T4) - Triiodothyronine (T3) → Approximately 90% of the thyroid hormone is in the form of T4, whereas 10% is T3 Source: Clinical Chemistry. 2010. Kaplan and Pesce. Mosby.
  • 46. Thyroid •Follicle = sac of stored hormone Makes thyroglobulin Contains thyroglobulin with attached iodine molecules
  • 47. 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 by osteolasts (lowers blood levels of Calcium)
  • 48. Thyroid Gland Trap dietary iodine TSH stimulation Synthesize thyroglobulin + thyroid peroxidase
  • 49. 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
  • 50. Parathyroid • 4 pea-sized glands found on back of thyroid gland
  • 51. PARATHYROID GLANDS • PTH: increases serum calcium and decreases serum phosphate • PTH=Phosphate Trashing Hormone • 1. Increase bone reabsorption of calcium • 2. Increase kidney reabsorption of calcium • 3. Decrease kidney reabsorption of phosphate • 4. Increase Vitamin D production by stimulating kidney (thus, indirect increase in intestinal calcium)
  • 52. Parathyroid hormone (PTH) & Calcitonin (CT)
  • 54. ADRENAL GLANDS • Two adrenal glands located on top of each kidney; each has two parts – Cortex • Mineralocorticoids • Glucocorticoids Regulation the three S’s Salt, sugar and sex • Androgens – Medulla • epinephrine • norepinephrine
  • 59. Adrenal Gland: Aldosterone
  • 60. Glucocorticoid: Cortisol • Glucose formation: gluconeogenesis (prime effect) • Breakdown of protein • (increase release of amino acids into blood stream) • Breakdown of fat (lipolysis) • Depression of Immune function • (Prescribed for organ transplants) • Anti-Inflammatory effects • (inhibit WBC’s but also retard tissue repair) • Resistance to stress: Provide tissues with a ready supply of ATP
  • 61. Adrenal Gland: Cortisol Normally cortisol is present in the body at higher levels in the morning, and at its lowest at night.
  • 62. Adrenal Gland: Cortisol
  • 63. Categories of Endocrine Disease • Hyposecretion • Hypersecretion • Target cell hyporesponsiveness
  • 64. Categories of Endocrine Disease • Hyposecretion – Primary hyposecretion occurs when an ENDOCRINE GLAND releases an inadequate amount of hormone to meet physiologic needs – Secondary hyposecretion occurs when secretion of a TROPIC HORMONE is inadequate to cause the target gland to secrete adequate amounts of hormone
  • 65. Categories of Endocrine Disease (Cont.) • Hypersecretion – Primary hypersecretion occurs when there is a DYSFUNCTION OF THE ENDOCRINE GLAND that results in abnormally high secretion of hormone – Secondary hypersecretion occurs when there is an ELEVATION IN THE TROPIC LEVEL of one hormone that results in an increased plasma concentration of the endocrine gland hormone also
  • 66. Categories of Endocrine Disease • Target cell hyporesponsiveness – Typically due to lack of or a deficiency in cellular receptors, but can occur with postreceptor mechanisms, such as second-messenger dysfunction that causes decreased cellular response – Hormone resistance of the target tissues will cause the same set of clinical symptoms as hyposecretion