Introduction to neuroendocrinology

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Introduction to neuroendocrinology
or the tip of the tip of a BIG iceberg
Dr. Arturo E. Gonzalez-Iglesias

• Current Topics Workshop on Mathematical
  Neuroendocrinology
• Mathematical Biosciences Institute
• The Ohio State University
• August 9-13, 2010

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CENTRAL NERVOUS SYSTEM (CNS) Brain, Spinal cord
PERIPHERAL NERVOUS SYSTEM (PNS) Cranial nerves
and Spinal nerves
SENSORY (AFFERENT) DIVISION Somatic and visceral
nerve fibers
MOTOR (EFFERENT) DIVISION Motor nerve fibers
SYMPATHETIC DIVISION fight or flight
AUTONOMIC NERVOUS SYSTEM (ANS) Visceral motor
(involuntary)
SOMATIC NERVOUS SYSTEM (SNS) Somatic motor
(voluntary)
PARASYMPATHETIC DIVISION (Housekeeping)
Skeletal muscles
Cardiac muscles Smooth muscles GLANDS!
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GLANDS
Exocrine Glands
Endocrine Glands
Pituitary gland, gonads (ovary, testes), thyroid
gland, parathyroid gland, Adrenal
gland, LIVER, DUODENUM STOMACH PANCREAS
Sweat glands, salivary glands, mammary glands,
DUODENUM, LIVER, STOMACH PANCREAS
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Historical Notes

• Exocrine secretions were known by Hippocrates and
  ancient Romans
• The endocrine secretions were first identified at
  the turn of the 20th century. The first to speak
  about internal secretions, that is, secretions
  released into the blood circulations, was the
  French physiologist CE Brown-Sequard (1817-1894).
  

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Historical Notes Continued

• Brown-Sequard suggested that the internal
  secretions influence general metabolism, muscle
  strength, reproductive and brain function.
• He also suggested that when the internal
  secretion products were diminished -- as with
  aging -- some of the functions they regulated
  were lost.
• But, replacement therapy would restore the lost
  functions.

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Claude Bernard (1855) although the liver
produced an external secretion (bile), it also
emitted an INTERNAL SECRETION directly into the
BLOODSTREAM
von Mering and Minkowski (1889) . Diabetes did
not follow simple ligation of the pancreatic duct
ligation but would occur if the pancreas was
resected the pancreas acted as a DUCTLESS
GLAND
Bayliss and Starling (1902) isolated the first
hormone SECRETIN They referred to it as a
chemical messenger until they coined the term
HORMONE in 1905.
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HORMONE to stimulate, to arouse, to send a
message
ENDOCRINE to secrete internally
Internal secretions serve to coordinate body
functions Brown-Sequard and dArsonval
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maintaining the internal stability of an organism
HOMEOSTASIS standing at about the same level
Only possible through multiple dynamic
equilibrium adjustment and regulation mechanisms
ALLOSTASIS remaining stable by being
variable Process of achieving stability
(homeostasis) through physiological or behavioral
change. Dynamic balance of a variety of systems
adapting their functioning
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Kopec S (1922) Studies on the necessity of the
brain for the inception of insect metamorphosis.
Biol. Bull. Woods Hole, 1701. 42, pp. 323-34.
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HYPOTHALAMUS regulates the internal milieu of the
cells within narrow limits as it compensates for
changing external conditions by controlling the
nervous system and the endocrine system
HYPOTHALAMUS exerts control over the endocrine
system through the PITUITARY GLAND
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PITUITARY DEVELOPMENT
Early in gestation a finger of ectoderm grows
upward from the roof of the mouth. This
protrusion is called Rathke's pouch and will
develop into the anterior pituitary or
adenohypophysis.
At the same time, a finger of neuroectodermal
tissue (the infundibulum) evaginates ventrally
from the diencephalon of the developing brain to
become the posterior pituitary or neurohypophysis.
As the pouch contacts the infundibulum, it begins
to pinch off from its connection with the oral
cavity. The pouch normally closes but a remnant
often persists as a cleft.
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pituita phlegm, mucus
Conrad V. Schneider of Wittenburg (1655)
openings of the ethmoid bone are for olfactory
nerves Richard Lower of Oxford (1670) no fluid
appeared in the nasal cavities after greatly
increasing intraventricular fluid through
injection of water into jugular veins of cadavers
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Le Comte (1898) pituitary enlarges during
pregnancy
HYPOPHYSECTOMY
G.Vassale and E. Sacchi (1892) Perturbed fluid
metabolism
X
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Le Comte (1898) pituitary enlarges during
pregnancy
HYPOPHYSECTOMY
G.Vassale and E. Sacchi (1892) Perturbed fluid
metabolism
X
Thyroid atrophy (B Aschner, 1912)
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Le Comte (1898) pituitary enlarges during
pregnancy
HYPOPHYSECTOMY
G.Vassale and E. Sacchi (1892) Perturbed fluid
metabolism
X
Thyroid atrophy (B Aschner, 1912)
Adrenal atrophy (G.Ascoli and T. Legnani, 1912)
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Le Comte (1898) pituitary enlarges during
pregnancy
HYPOPHYSECTOMY
G.Vassale and E. Sacchi (1892) Perturbed fluid
metabolism
X
Thyroid atrophy (B Aschner, 1912)
Adrenal atrophy (G.Ascoli and T. Legnani, 1912)
Ovary and uterus (Crowe, Cushing and Homans, 1910)
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Le Comte (1898) pituitary enlarges during
pregnancy
HYPOPHYSECTOMY
G.Vassale and E. Sacchi (1892) Perturbed fluid
metabolism
X
Thyroid atrophy (B Aschner, 1912)
Adrenal atrophy (G.Ascoli and T. Legnani, 1912)
Ovary and uterus (Crowe, Cushing and Homans, 1910)
PITUITARY EXTRACTS RESTORED FUNCTIONS!!
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WHAT SUBSTANCES?
WHAT CELLS?
WHAT FUNCTIONS?
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Schonemann (1892) distinction among
acidophils, basophils and chromophobes in
pituitaries stained with hematoxylin and eosin.
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ANTERIOR PITUITARY CELL TYPES AND HORMONES
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ANTERIOR PITUITARY CELL TYPES AND HORMONES
Ovaries Estradiol Progesterone
Testes Testosterone DHT
Direct growth effects, IGF-1 in liver
Lactogenesis
Glucocorticoids Mineralocorticoids Adrenal
androgens
Metabolism Triiodothyronine Thyroxine
Melanin, pigmentation
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ANTERIOR PITUITARY CELL TYPES AND HORMONES
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FEEDBACK CONTROL OF ANTERIOR PITUITARY HORMONES
Feedback circuits are at the root of most control
mechanisms in physiology. They are particularly
prominent in the endocrine system.
(-)
ANTERIOR PITUITARY GLAND
Anterior Pituitary hormone
()
Instances of positive feedback certainly occur,
but negative feedback is much more common.
PERIPHERAL ENDOCRINE GLAND
Peripheral gland hormone
()
Targets
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PERIPHERAL CONTROL OF GONADOTROPHINS
(-)
ANTERIOR PITUITARY GLAND
FSH
LH
()
Activin
OVARY
Inhibin
ESTRADIOL, PROGESTERONE
()
WIDESPREAD
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PERIPHERAL CONTROL OF ADRENOCORTICOTROPIC HORMONE
(ACTH)
(-)
ANTERIOR PITUITARY GLAND
ACTH
()
ADRENAL CORTEX
Gluco- and mineralo- corticosteroids Androgenic
steroids
Widespread
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PERIPHERAL CONTROL OF ADRENOCORTICOTROPIC HORMONE
(ACTH)
(-)
ANTERIOR PITUITARY GLAND
ACTH
()
ADRENAL CORTEX
Cushing syndrome
Gluco- and mineralo- corticosteroids Androgenic
steroids
Widespread
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PERIPHERAL CONTROL OF ADRENOCORTICOTROPIC HORMONE
(ACTH)
()
(-)
ANTERIOR PITUITARY GLAND
Epinephrine Norepinephrine
ACTH
()
()
ADRENAL CORTEX
GLUCO- and mineralo- corticosteroids Androgenic
steroids
()
Widespread
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PERIPHERAL CONTROL OF THYROID-STIMULATING HORMONE
(TSH)
(-)
ANTERIOR PITUITARY GLAND
TSH
()
THYROID GLAND
Triiodothyronine (T3) Thyroxine (T4)
Widespread metabolism, growth, development, body
temperature, heart rate, etc
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PERIPHERAL CONTROL OF GROWTH HORMONE
(-)
ANTERIOR PITUITARY GLAND
Growth Hormone (GH)
()
LIVER
Insulin-like Growth Factor (IGF-1)
()
Bone, muscle, adipose tissues
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And, of course, there is also PROLACTIN
ANTERIOR PITUITARY GLAND
(-)
Prolactin (PRL)
()
MAMMARY GLAND, OVARY
Lactogenesis, Galactopoiesis, luteal function
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EXTRAPITUITARY PROLACTIN
PLACENTA, AMNION, DECIDUA, UTERUS
BRAIN
PRL
IMMUNE SYSTEM (THYMUS, SPLEEN)
MAMMARY GLAND
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PROLACTIN FUNCTIONS
PARENTAL BEHAVIOR
SEXUAL BEHAVIOUR
IMMUNITY
ANGIOGENESIS
OSMOREGULATION
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FEEDBACK CONTROL OF ANTERIOR PITUITARY HORMONES

• Pregnancy suppresses menstrual/estrous cycles.
  Removal of corpora lutea reestablishes the cycles.

• Castration leads to enlargement of anterior
  pituitary (gonadotropes)

• Menopause

Gonadal steroids
LH, FSH

• Graves disease (autoimmune hyperthyroidism)

T3, T4
TSH

• Hashimoto's thyroiditis

T3, T4
TSH

• Primary Addisons disease darkening of the skin

Corticosteroids
ACTH, MSH
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HYPOTHALAMUS regulates the internal milieu of the
cells within narrow limits as it compensates for
changing external conditions by controlling the
nervous system and the endocrine system
HYPOTHALAMUS exerts control over the endocrine
system through the PITUITARY GLAND
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Hypothalamic nuclei
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How is the Hypothalamus connected to the
Posterior Pituitary?
Through the Hypothalamo-Hypophyseal tract
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How is the Hypothalamus connected to the Anterior
Pituitary?
Through the Hypothalamo-Hypophysial portal system
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The Hypothalamo-Hypophysial portal system
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The Hypothalamo-Hypophysial portal system
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The Hypothalamo-Hypophysial portal system
Popa GT and Fielding U (1930) Journal of Anatomy
67 (Pt2) 227-233
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The Hypothalamo-Hypophysial portal system
Houssay, BA Biassotti, A and Sammartino R
(1935). Rev Soc Arg Biol 11318-330