Case W4544

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IGP Endocrinology 2003
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The Ancients

• It seems likely that the first endocrinologic
  manipulation performed on humans or animals was
  castration of males.
• By the 4th century B.C. the physiologic
  consequences were well known
• This procedure was performed to create court
  eunuchs and as punishment for prisoners

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Beginnings

• Around 1766 Albrecht Von Haller proposed that
  the thymus, thyroid, and spleen were ductless
  glands that poured a special substance into the
  veins

• In 1855 Claude Bernard introduced the term
  internal secretions. He distinguished hepatic
  biliary secretion (externalinto a duct) from
  hepatic glucose production (internalinto the
  bloodstream)

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Organs Without Known Functions

• First anatomic description of glandulae renae
  incumbentes by Bartolomeo Eustachius in 1563
  (discovered and published by Lancisi in1714

• In 1716 the Academie des Sciences de Bordeaux
  offered a prize for the discovery of the purpose
  of the adrenals. Charles de Montesquieu judged
  the entries unsatisfactory and awarded no prize.

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Human Disease Associated With Glandular Pathology
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Charles Eduoard Brown-Sequard Confirms Addisons
Clinical Observation

• Surgical removal of the adrenal glands of
  animals was incompatible with life
• Neither Addisons nor Brown-Sequards findings
  are rapidly accepted.

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The Identity of The Adrenal Hormone Remains
Obscure
I have worked out the disease If it be
remediable, nature, with fair play, will remedy
it T. Addison
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Isolation of Insulin, The Product of Pancreatic
Islet ? Cells
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Chemical Isolation of the Products of the Adrenal
Cortex
From the 1920s to the 1940s the application of
modern chemical purification techniques permitted
the isolation of cortisol as the active hormonal
compound of the adrenal cortex.
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Normal Thyroid Function is Essential to Health

• Sir William Gull provided an early clinical
  description (1873) of the appearance of persons
  with hypothyroidism
• In 1914 Edward Kendall successfully isolated
  thyroxine, and the compound was successfully used
  to patients with defective thyroid function

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Classic Endocrine Glands and Their Products (
peptide and nonpeptide)

• Thyroid
• Adrenal
• Gonads
• Pancreatic Islets
• Parathyroids

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Pituitary Peptide Hormones Regulate Target Gland
Function

• 1887Oscar Minkowski recognizes acromegaly
  associated with a pituitary tumor
• 1910 Harvey Cushing shows pituitary necessary
  for reproductive function
• 1912B Aschner observed atrophy of the thyroid
  in hypophysectomized animals
• 1932 Harvey Cushing describes adrenal
  hyperplasia and cortisol excess caused by
  pituitary tumors

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Purification of Hypophyseal Peptide Hormones
Establishes Their Chemical Identities

• 1940 -- Luteinizing Hormone
• 1943 Adrenocorticotropin
• 1945 Growth Hormone
• 1949 -- Follicle Stimulating Hormone

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Hypothalamic Peptides Regulate Anterior Pituitary
Hormone Release

• Thyrotropin Releasing Hormone
• Gonadotropin Releasing Hormone
• Growth Hormone Releasing Hormone
• Corticotropin Releasing Hormone

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Two Hypothalamic Products Inhibit Anterior
Pituitary Hormone Release

• Somatostatin (GH)
• Dopamine (Prolactin)

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Feedback Inhibition at the Hypothalamus and
Pituitary by Hormonal Products
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Summary and Challenge

• We have taken a look at the classical
  endocrine system from an historical perspective
• Our present conception of the borders of
  endocrinology are now blurred. Is it glands? Is
  it signaling molecules? Does it include
  paracrine or autocrine effects?
• We now realize that many nonglandular tissues
  make classical hormones (e.g., the brain, the
  heart, and the thymus make steroids).
• We also realize that other tissues (e.g., fat)
  make molecules that are secreted into blood and
  signal at a distance from their cells of origin
  (e.g. leptin)

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The PlanA Closer Look At

• The brain as a source of peptide hormones
• A hormonal signaling system that controls body
  weight
• How thyroid/steroid and related hormones work
• Paracrinology and autocrinology
• Insulin and glucagon physiology and molecular
  biology
• Diabetes mellitus

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