Hypothalamus and its hormones, hormones of the pituitary gland

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Hypothalamus and its hormones, hormones of the
pituitary gland

• Romana Šlamberová, M.D. Ph.D.
• Department of Normal, Pathological and Clinical
  Physiology

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The hypothalamus

• Hormonal (anterior portion) or nervous (posterior
  portion) control of the pituitary gland
• Hormones control secretion of hormones in the
  anterior pituitary
• Releasing hormones (factors)
• Inhibitory hormones (factors)
• Hormones secreted and transported to anterior
  pituitary through hypothalamic-hypophysial
  vessels to pituitary sinuses
• Nerves Magnocellular neurons in the supraoptic
  and paraventricular nuclei of the hypothalamus
  axoplasm transport of hormones from the
  hypothalamus to the posterior pituitary

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Hypothalamic-hypophysial portal system (1)

• Special neurons in the hypothalamus synthesize
  and secrete the hypothalamic releasing and
  inhibitory hormones that control secretion of
  anterior pituitary
• These neurons originate in various parts of the
  hypothalamus and send their nerve fibers to the
  median eminence and tuber cinerreum (extension of
  hypothalamic tissue into the pituitary stalk)
• Hormones are secreted to the tissue fluids,
  absorbed into the hypothalamic-hypophysial portal
  system and transported to the sinuses of the
  anterior pituitary

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Hypothalamic hormones controlling anterior
pituitary gland (1)

• Major hypothalamic releasing hormones
• Thyreotropin-releasing hormone (TRH) causes
  release of thyroid stimulating hormone (TSH)
• Corticotropin-releasing hormone (CRH) causes
  release of adrenocorticotropin hormone (ACTH)
• Growth hormone releasing hormone (GHRH) causes
  release of growth hormone
• Gonadotropin releasing hormone (GnRH) causes
  release of the 2 gonadotropic hormones
  (luteinizing and follicle-stimulating hormone)

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Hypothalamic hormones controlling anterior
pituitary gland (2)

• Major hypothalamic inhibitory hormones
• Growth hormone inhibitory hormone (GHIH)
  SOMATOSTATIN inhibits release of growth hormone
• Prolactin inhibitory hormone (PIH) inhibits
  prolactin secretion

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The pituitary gland

• 1 cm in diameter
• 0.5 1 g in weight
• In sella turcica (bony cavity at the base of the
  brain
• Connected to the hypothalamus via pituitary stalk
• Parts
• Adenohypophysis anterior
• Neurohypophysis - posterior
• Pars intermedia (almost absent in humans)

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Hormones of the adenohypophysis(1)

• Human growth hormone (hGH) affects protein
  formation, cell multiplication, cell
  differentiation
• Adrenocorticotropin (ACTH) controls secretion
  of some of the adrenocortical hormones (affects
  metabolism of glucose, proteins and fats)
• Thyroid-stimulating hormone (STH) controls
  secretion of thyroxine and triodothyronine by the
  thyroid gland (controls rates of most
  intercellular chemical reactions of the entire
  body)
• Prolactin promotes mammary gland development
  and milk production
• Follicle-stimulating hormone (FSH) and
  Luteinizing hormone control growth of the
  ovaries and testes and their hormonal and
  reproductive functions

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Hormones of the adenohypophysis(2)

• Other hormones of adenohypohysis
• ß-Lipotropin (ß-LPH) function unknown
• ?-Melanocyte-stimulating hormone (?-MSH)
  stimulates melanin synthesis in melanocytes

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Cell types in the anterior pituitary

• Chromophobes mostly inactive cells with only
  few secretory granules
• Chromophils active secretory cells
• Acidophils (stained with acidic dyes)
• Basophils (stained with basic dyes)

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Hormones of Intermediate lobe

• Melanocytes stimulating hormones (MSH) types a,
  ß, ?.
• In humans stimulate melanin synthesis in
  melanocytes
• In fish, amphibians and reptiles expand
  melanophores
• ?- Lipotropin (?LPH) and Corticotropin-like
  intermetiate lobe peptide (CLIP)
• From prehormone POMC (pro-opiomelanocortin)
• Function unknown

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Hormones of the neurohypophysis

• Magnocellular neurons (long neurons) located in
  the supraoptic and paraventricular nuclei of the
  hypothalamus axoplasm transport of hormones
  from the hypothalamus to the posterior pituitary
• Hormones Polypeptides with 9 amino acids
• ADH (vasopressin) Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg
  -GlyNH2
• Oxytocin Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-GlyNH2
• Similar structure, similar action

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Cell types in the posterior pituitary

• Pituicytes glial-like cells
• no hormone secretion
• supporting structure for terminal nerve fibers
  and endings
• Axons of secretory neurons located in the
  supraoptic and paraventricular nuclei of the
  hypothalamus

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ADH (vasopressin)

• Formed primarily in the supraoptic nuclei
• Regulates water excretion by the kidneys
• Increases the permeability of collecting tubules
  and ducts to water - water reabsorption
  concentrated urine
• Osmotic regulation osmoreceptors in the
  hypothalamus or somewhere near
• Causes vasoconstriction
• Constrict arterioles throughout the entire body
• Blood volume (activated when decreased blood
  volume)
• stretch (volumoreceptors) in right atrium of
  the heart
• - baroreceptors in carotid, aortic and pulmonary
  regions

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Oxytocin

• Formed primarily in the paraventricular nuclei
• Causes contraction of the pregnant uterus
• Oxytocin plasma levels increase in the last stage
  of labor
• Cervix stimulation during labor elicit nervous
  signals to hypothalamus and the secretion of
  oxytocin increases
• Aids the milk ejection by the breasts
• The suckling stimuli cause signals to be
  transmitted through sensory nerves to the
  oxytocin neurons in the PV and SO nuclei of the
  hypothalamus.
• Oxytocin causes contraction of myoepithelial
  cells around the alveoli.
• In less than a minute after suckling started the
  milk begins to flow.

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Growth hormone (somatotropic hormone,
somatotropin)

• Chemical structure small protein (191 amino
  acids)
• Function hGH enhances body protein, uses up the
  fat stores and conserves carbohydrates
• Increases rate of protein synthesis in most cells
  of the body
• Increases mobilization of fatty acids in the
  blood and increases use of the fatty acids for
  energy
• Decreases rate of glucose utilization throughout
  the body

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hGH - Function (1) Increase in protein deposition

• Enhancement of amino acid transport through the
  cell membrane to the interior of the cells (more
  AAs available for protein synthesis)
• Enhancement of RNA translation to cause protein
  synthesis by the ribosomes (even when the AAs
  concentration are not increased)
• Increase in nuclear translation of DNA to form
  RNA
• Decrease in catabolism of protein and amino acids

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hGH - Function (2) Increase in fat utilization
for energy

• Causing release of fatty acids from adipose
  tissue (increase in fatty acid concentration in
  the body fluid)
• Enhancement of conversion of fatty acids to
  acetyl coenzyme A (subsequent utilization of it
  for energy)
• Ketogenic effect of hGH ketosis may occur when
  the amount of hGH is too high and causes great
  mobilization of fatty acids from adipose tissue
  that requires large amount of acetoacetic acid
  formed by the liver (may cause fatty liver)

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hGH - Function (3)Decrease in carbohydrate
utilization

• Decrease in glucose uptake in tissues (skeletal
  muscle and fat)
• Increase in glucose production by the liver
• Increase in insulin secretion
• hGH has DIABETOGENIC EFFECT
• growth hormone-induced insulin resistance
  attenuates insulins actions, such as
• To stimulate uptake and utilization of glucose in
  skeletal muscle and fat
• To inhibit glucose output by the liver
• This leads to increase of glucose concentration
  in the blood and compensatory increase of
  insulin.
• Excess in hGH may cause metabolic disturbance
  similar to those found in patients with DM II.

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hGH stimulates cartilage and bone growth

• Cartilages and bones are the main tissues of hGH
  action
• Increased deposition of protein by the
  chondrocytic and osteogenic cells that cause bone
  growth
• Increased rate if reproduction of these cells
• Specific effect of converting chondrocytes into
  osteogenic cells (causing specific deposition of
  new bone)
• 2 principle mechanisms of bone growth
• Growth in length (during development before
  closing the epiphysal slit)
• Growth in width (also after adolescence) hGH
  stimulates osteoblasts

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Somatomedins

• Secreted by the liver and other tissue based of
  the hGH stimulation
• Similar effect as insulin IGF (insulin-like
  growth factors)
• Function support the action of hGH (unclear is
  if the hGH may act without somatomedines or not)
• Types
• Somatomedin C IGF I
• IGF II

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Regulation of hGH secretion(1) - stimulation

• hGH is secreted in pulsation increasing and
  decreasing
• Factors stimulating secretion
• Starvation (especially with protein deficiency)
• Hypoglycemia
• low fatty acids in the blood
• Exercise
• Excitement
• Trauma
• The first 2 hrs of deep sleep (non-REM)
• Hormones
• GHRF Growth hormone releasing factor
• Estrogens and androgens

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Regulation of hGH secretion(2) - inhibition

• Factors inhibiting secretion
• Hyperglycemia
• High fatty acids in the blood
• Aging
• Obesity
• REM sleep
• Hormones
• GHIH Growth hormone inhibitory hormone
  (Somatostatin)
• Exogenous growth hormones
• Somatomedins (IGF)

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Abnormalities of hGH secretion(1) - hypofunction

• Panhypopituitarism decrease of secretion of all
  anterior pituitary hormones
• Congenital
• Induced by tumor that destroys the gland
• Dwarfism
• Decrease of all or more than 1 hormone of
  anterior pituitary (the person does not reach
  sexual maturation missing gonadal hormones)
• Decrease just in hGH only smaller person, but
  can maturate
• Missing somatomedins
• Panhypopituitarism in the adulthood
• Due to tumor or trombosis of the pituitary blood
  vessels
• Results in hypothyroidism, decrease in
  glucocorticoids, suppression of gonadotropic
  hormones

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Abnormalities of hGH secretion(2) - hyperfunction

• Gigantism increased growing (randomly) giants
• Due to increased activity of somatotropes or
  tumor during development
• Giants have hyperglycemia (DM)
• Acromegaly increased growing of acral parts of
  the body
• Due to increased activity of somatotropes or
  tumor after puberty (after closure the epiphysal
  slits)
• Bones grow only to thickness ( enlargement of
  hands and feet, membranous bones such as cranium,
  nose, supraorbital ridges, chin etc.