The hypothalamus as endocrine organ

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The hypothalamus as endocrine organ
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Pituitary It is anatomically well defined and
was know by the early physicians Galen regarded
the pituitary as the gland that treated the waste
product from distillation of animal spirit The
pituitary importance in the development of the
corpora lutea of the female rabbit after
pregrancy was demonstrated in the 1920s Less
importance was given to the hypothalamus
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Some details on the History of the
hypothalamus The hypothalamus was started to be
studied in the 1920, when it was better defined
anatomically but whose function was yet
unknown In the early decades of the 1900 it was
shown that the adiposogenitale syndrome (a
condition associated with reduced development of
the genitals, mental retardation, polyuria
production of too much urine- and polydipsia
too much thirst- is not caused by a disfunction
of the pituitary but rather by a disfunction of
the hypothalamus. The demonstration was
performed by inducing it by damaging the
hypothalamus (and not the pituitary) in a precise
point, in an animal model.
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History of the hypothalamus (contd)

• Demonstration of the hypothalamus-pituitary
  association
• Only in the second half of the 1900 were the
  pituitary hormones studied more systematically,
  with the discovery of the pituitary release of
• Growth hormone
• Thyroid stimulating hormone
• Adrenal stimulating hormone
• gonad stimulating hormone
• The concept of (negative) feedback for shutting
  down pituitary hormone release was also parallely
  developed
• The presence of the hypothalamus as pituitary
  activating center was realized after experiments
  showed the absence of this negative feedback when
  the pituitary was dislodged and re-lodged
  (transplanted) far from the hypothalamic blood
  torrent
• These experiments suggested that the hypothalamus
  and the pituitary are functionally related

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History of the hypothalamus (contd) In the 1930
the development of submillimetric stereotactic
techniques allowed the advancement of the
knowledge on hypothalamic function Animal model
research showed that stimulation of precise
nuclei in the hypothalamus produces peculiar
behavior Using new anatomical techniques, Ernst
and Berta Sharrer propose that granule containing
cells, like those found in the supraoptic
nucleus, are responsible for hormone production
and release. In fact, cut of the hypophysial
stalk separating the hypothalamus from the
pituitary, makes granules accumulate on the
distal end of the cells Further experiments on
the rabbit development of corpora lutea, which
change after the female become pregnant, showed
again that the pituitary cannot induce the
transofrmation alone, but it needs to be
connected to the hypothalamus to carry out its
function During this and other series of
experiments was also shown that the antidiuretic
hormone was produced by the suprachiasmatic
nucleus (hypoth) , transported by the long axons
reaching the posterior pituitary, and the
posterior pituitary hormones vasopressin and
oxytocin were identified
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NEUROVASCULAR LINK
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History of the hypothalamus (contd)
NEUROVASCULAR LINK
Green and Harris studied the hypothalamic control
of the anterior pituitary by means of the portal
system, postulating precisely that pituitary
hormones are produced as a consequence of
hypothalamic release into the median eminence and
carried by the portal system to the anterior
pituitary 1 The hypothalamus produces
substances that act on cells of the anterior
pituitary 2 These substances are carried to the
pituitary by the portal system It also became
clear in the same years that the hypothyalamus is
not exclusive in synthezising and releasing its
hormones, but also several other classes of cells
in the brain can produce the same hormones Today
we also know most of the genes that produce
hypothalamic as well as pituitary peptide
hormones, prehormones and pre-propeptides
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Anatomy of posterior posterior pituitary
Hormones vasopressin and oxytocin, piuitary
axons directly from hypothalamus
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• List of Hypophysiotropic hormones
• (released by the hypothalamus and acting on the
  pituitary)
• Corticotropin releasing hormone (CRH)
• Gonadotropin releasing hormone (GnRH) or
  Lutenizing hormone releasing hormone (LHRH)
• Growth hormone releasing hormone (GHRH)
• Somatotropin release-inhibiting hormone (SRIH)
• Thyrotropin releasing hormone (TRH)
• Prolactin release inhibiting factor (PIF)
• Only immunocytochemistry provides precise
  indication of the localization of the hormone
  producing cells

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Vascular-mediated hypothalamic control of
anterior pituitary hormones
Anterior pituitary
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• Corticotropin releasing hormone (CRH)
• Produced by
• Paraventricular nuclei (parvocellular nucleus)
• Supraoptic
• Medial
• Periventricular preoptic
• Premammillary
• Also by several extrahypothalamic regions
• Coreleased with
• Vasopressin
• Neurotensin
• Enkephalin
• GABA
• The paraventricular nucleus has multiple crossed
  projections between CRH-CRH producing cells, but
  also between the other cells producing other
  hormones (oxytocin and vasopressin)

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• Gonadotropin releasing hormone (GnRH) or
  Lutenizing hormone releasing hormone(LHRH)
• Septal preoptic-suprachiasmatic region
• Mediobasal area of tuber cinereum infundibular
  and premammillary nuclei
• Other brain areas also produce GnRH (olfactory
  bulb, hippocampus)
• 70 of GnRH producing neurons project to the
  medial eminence (and then to pituitary)
• 30 of them project to other targets in the brain
• The two population are not separate and GnRH
  producing neurons are interconnected with
  themselves
• The are modulated by
• NPY
• NT
• CRH
• VP
• Galanin
• NOT by sex steroids

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• Growth hormone (somatotropin)-releasing hormone
  GHRH
• Definition Growth hormone (released by the
  pituitary) somatotropin
• -Produced in the arcuate nucleus and
• Medial perifornical region of lateral
  hypothalamus, but there are also other nuclei
  with low density of GHRH producing cells
• Co-released with dopamine or galanin
• GHRH-producing cells are modulated by TRH, subP,
  enkephalins, monoamines

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• Somatostatin, or Somatotropin release-inhibiting
  hormone (SRIH)
• SRIH is produced in
• -Periventricular nuclei (hypoth)
• -other hypothalamic areas
• Pancreas
• Guts
• Other parts of the brain different from hyopth
• Neocortex, amygdala, hippocampus, septum,
  brainstem
• Autosynapses
• Its release is modulated by
• CRH
• NPY
• GABA

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• Thyrotropin releasing hormone TRH
• First hypothalamic hormone characterized
• Widely distributed inside and outside the brain
• Synthtized in parvocellular division of
  paraventricular nucleus, preoptic nucleus,
  dorsomedial, laterobasal
• Outside the hypothalamus
• Raphe, olfactory bulb, diagonal band of Broca,
  septum
• TRH release is modulated by
• NPY
• Proopiomelanocortin
• Norepinephrine
• Serotonin
• Autosynapses
• Prolactin-inhibiting factor (PIF) (dopamine)

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Many types of feedback. Two of them are Short
and ultrashort Short back from anterior
pituitary Ultrashort from hypophysiotropic
hormones secreted by the hypothalamus itself
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• Hypothalamic input and output channels
• Output
• Humoral output (through portal system, previously
  discussed)
• Neural output (to brain and spinal cord
  structures)
• Input
• Humoral input (feedback from body glands through
  blood)
• Neural inputs (from
• Amygdala
• Hippocampus
• Septum
• Thalamus
• Basal ganglia
• Cortex
• Lower brainstem
• - Spinal cord

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Hypothalamic input and output channels brain
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Hypothalamic input and output channels body
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• Neuroendocrinology and immunology
• Original observation the thymus, which is
  responsible for the activation of immune cells
  producing antibodies, is involved in stress
  response (controlled by the hypothalamus-hypophysi
  s-adrenal gland response
• Abundant new information links neuroendocrine and
  immune response
• Peptide hormones are produced by the immune
  system
• Hormones and neurohormones are involved in immune
  system regulation
• Cytokines produced by the immune system affect
  the neuroendocrine system

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Reciprocal interaction between neuroendocrine and
immune system
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• Neuroendocrinology related fields
• Many fields in neuroscience have bloomed after
  the advances in neuroendocrinology
• Neurochemistry
• Neuropharmacology
• - Neuropsychology
• - Neuropathology
• - Developmental Neurobiology
• - Social behavior
• - Learning and memory
• Maternal behavior
• Sexual behavior
• Nociception
• Rewarded behavior
• Drug tolerance