THE ENDOCRINE SYSTEM

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THE ENDOCRINE SYSTEM

• D. C. MIKULECKY
• PROFESSOR OF PHYSIOLOGY
• AND
• FACULTY MENTORING PROGRAM

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COMPARISON OF ENDOCRINE AND NERVOUS SYSTEMS

• NERVOUS SYSTEM
• WIRED
• CHEMICAL SIGNAL AT TARGET CELL
• RAPID
• BRIEF DURATION
• CLOSE ANATOMICAL PROXIMITY

• ENDOCRINE SYSTEM
• WIRELESS
• CHEMICAL SIGNAL AT TARGET CELL
• SLOW
• LONG DURATION
• SPECIFIC RECEPTORS

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WHAT IS A SIGNAL?

• SEMIOTICS
• INFORMATION THEORY
• NERVOUS SYTEM
• ENDOCRINE
• PARACRINE
• ENDOCRINE
• ANTIBODIES AND OTHER FOREIGN SUBSTANCES
• PARALLEL PROCESSING

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CHEMICAL SIGNALS

• SIGNALING MOLECULE IS SECRETED
• TRAVELS FRON ONE SITE TO ANOTHER
• RECEPTOR AT TARGET
• BINDING TO RECEPTOR EFFECTS SOME CHANGE

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ELEMENTS OF CELL SIGNALLING MECHANISMS

• SIGNAL MOLECULES
• RECEPTORS
• SIGNAL TRANSDUCTION

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SIGNAL MOLECULES (FIRST MESSENGERS)

• NEUROTRANSMITTERS
• HORMONES
• LOCAL MEDIATORS

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EXAMPLES OF SIGNALLING MOLECULES
(SEE TABLE 1 IN TEXT)
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RECEPTORS

• CELL MEMBRANE HYDROPHILIC SIGNAL MOLECULES
  (POLYPEPTIDES, CATECHOLAMINES)
• CYTOPLASMIC HYDROPHOBIC SIGNAL MOLECULES
  (STEROIDS, VITAMIN D, THYROID HORMONE)

BOUND TO CARRIER PROTEIN
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LIGANDS, AGONISTS AND ANTAGONISTS

• LIGANDS BIND TO RECEPTORS IN A SPECIFIC MANNER
• LIGANDS THAT ELICIT A PHYSIOLOGICAL RESPONSE ARE
  AGONISTS
• LIGANDS THAT OCCUPY THE RECEPTOR BUT ELICIT NO
  RESPONSE ARE ANTAGONISTS (OR BLOCKERS)

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EXAMPLES OF ANTAGONISTS

• PROPRANOLOL BLOCKS THE EFFECTS OF CATECHOLAMINES
  BY BINDING TO THEIR RECEPTORS
• SPIRONOLACTONE BLOCKS ALDOSTERONE (DIURETIC)

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REGULATION OF RECEPTOR QUANTITY AS A CONTROL
MECHANISM

• DESENSITIZATION BY DOWNREGULATION DUE TO
  INCREASED ANTAGONIST LEVELS
• INTERNALIZATION OF COMPLEX BY ENDOCYTOSIS
• RECEPTOR SYNTHESIS (UPREGULATION)

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AN EXAMPLE OF RECEPTOR RECYCLING
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MEMBRANE RECEPTORSG-PROTEIN RECEPTOR SUPERFAMILY

• MORE THAN 250 MEMBERS
• SERPENTINE GLYCOPROTEINS LOOP BACK AND FORTH
  THROUGH MEMBRANE
• EXTRACELLULAR DOMAIN AMINO TERMINAL PEPTIDE AND
  THREE LOOPS (HYDROPHILIC REGIONS)
• IN THE MEMBRANESEVEN ALPHA HELICES OF ABOUT 25
  HYDROPHOBIC AA
• SEE FIG 8 IN TEXT

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CATEGORIES OF HORMONES

• PEPTIDES
• AMINES
• STEROIDS

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PEPTIDES

• HYDROPHILIC
• DISSOLVED IN PLASMA
• RECEPTOR ON CELL SURFACE
• cAMP OR CALCIUM AS SECOND MESSENGERS
• ACTIVATE SPECIFIC GENES TO INITIATE PROTEIN
  SYNTHESIS

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PEPTIDE HORMONES

• HYPOTHALAMIC
• PITUITARY
• PANREATIC
• PARATHYROID
• GI
• KIDNEY
• LIVER
• HEART

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AMINES

• THYROID HORMONE
• CATECHOLAMINES
• ALL DERIVED FROM AMINO ACID TYROSINE
• UNIQUE SYNTHETIC AND SECRETORY PATHWAYS

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STEROIDS

• LIPOPHILIC
• RECEPTOR IN CYTOPLASM
• ACTIVATE SPECIFIC GENES TO INITIATE PROTEIN
  SYNTHESIS
• ADRENAL CORTICAL
• GONADAL
• PLACENTAL

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PLASMA CONCENTRATION OF HORMONES

• DEPENDS ON RATE OF SECRETION
• NEGATIVE FEEDBACK
• NEUROENDOCRINE REFLEXES
• DIURNAL RHYTHMS

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TYPES OF ENDOCRINE DISORDERS

• HORMONE EXCESS
• HORMONE DEFICIENCY
• DECREASED RESPOSIVENESS OF RECEPTORS

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HYPOTHALAMUS AND POSTERIOR PITUITARY
NEUROSECRETORY NEURONS
HYPOTHALAMUS
VASOPRESSIN
POSTERIOR PITUITARY
OXYTOCIN
ANTERIOR PITUITARY
SYSTEMIC ARTERY
SYSTEMIC VEIN
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HYPOTHALAMUS AND ANTERIOR PITUITARY
NEUROSECRETORY NEURONS
HYPOTHALAMUS

• ANTERIOR
• PITUITARY
• TSH
• ACTH
• PROLACTIN
• GROWTH
• HORMONE
• LH
• FSH

POSTERIOR PITUITARY