Hypothalamic-Pituitary Axis

Hypothalamic-Pituitary Axis

Hypothalamic-Pituitary Axis

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Hypothalamic-Pituitary Axis

  • Essential connection between the brain and the endocrine system
  • Brain can influence many important bodily functions
  • Crucial for homeostasis

Hypothalamus

  • Diencephalon region of the brain, found at the base of the brain forming the floor and part of the sides of the third ventricle
  • No effective blood-brain barrier
  • Contains several groups of neurones secreting many hormones and neurotransmitters
  • Some hormones are released into the blood and affect the release of trophic hormones by the anterior pituitary
  • Other hormones are transported down axons to the posterior pituitary for release
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Hypothalamus

  • Many important functions:
    • controlling the intake of food and drink
    • sexual behaviour sleep-wake cycle
    • regulating blood pressure and heart rate
    • maintaining body temperature
    • modulating emotions
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Pituitary Gland

  • Pea-sized gland
  • Two sub-glands, anterior and posterior, separated developmentally and autonomically
  • Anterior pituitary develops from the roof of the embryonic mouth and posterior pituitary from the brain
  • Anterior lobe linked to the hypothalamus by portal blood vessels from the median eminence
  • The posterior lobe is linked by nerves descending in the median eminence from the hypothalamus
  • The hypothalamus and pituitary are connected via the pituitary or infundibular stalk
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Anterior Pituitary Hormones

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Posterior to Pituitary and Hypothalamus Hormones

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Properties of Hypothalamic Releasing Hormones

  • Pulsatile release
  • Made by neurones, delivered by the vasculature
  • Act on specific receptors on target cells in the anterior pituitary
  • Stimulate trophin synthesis
  • Can also inhibit trophin release
  • Release regulated by negative feedback
  • Hypothalamic releasing hormones:
    • GnRH and the control of the secretion of prolactin
    • CRH
    • TRH
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Control of Pituitary Secretions

Growth Hormone Releasing Hormone (GHRH)

  • GHRH stimulates the synthesis and release of growth hormone by specific receptors on somatotrophs
  • 44 amino acid peptide, N-terminal 29 amino acids necessary for biological action
  • Related to glucagon
  • Also found in the pancreas and upper intestine but physiological role unknown
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Somatotrophin Release Inhibiting Factor/Somatostat

  • Cyclic 14 amino acid peptide, also 28 amino acid peptide
  • Receptor-mediated inhibition of the action of GHRH on somatotrophs
  • Can also inhibit secretion of TSH and prolactin by the pituitary
  • Found in many other areas of the brain and the body including the GI tract and pancreas
  • Suppresses the release of glucagon and insulin
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Anterior and Posterior Pituitary Hormones

  • Anterior pituitary
    • LH, FSH and prolactin
    • ACTH
    • TRH
    • Growth hormone
  • Posterior pituitary
    • Oxytocin
    • Vasopressin
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Anterior Pituitary Hormones and Their Targets

Growth Hormone

  • The most abundant anterior pituitary hormone, 191 amino acid peptide
  • Somatotropes make up 50% of secreting cells
  • Pulsatile secretion, two peaks in cycle, rises during first hour of sleep, levels highest at night
  • Levels highest during early childhood, also puberty (essential for gonad development), decline into adulthood
  • Interactions with other hormones such as glucocorticoids which promote production of proteins involved in effects of growth hormone
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Control of Growth Hormone Release

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Control of Growth Hormone Release

  • Release stimulated by growth hormone releasing hormone
  • Stress (hypoglycaemia, cold, surgery, severe exercise), onset of deep sleep and increased blood levels of arginine or leucine all promote release
  • Release inhibited by somatostatin 
  • Direct negative feedback by insulin-like growth factor-1 (IGF-1) on pituitary somtotrophs
  • IGF-1 stimulates somatostatin synthesis and secretion from the hypothalamus
  • Growth hormone may also act on the hypothalamus to either inhibit growth hormone release or increase somatostatin secretion
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Actions of Growth Hormone

  • Main actions
    • Linear growth of bone through effects on cartilage (long bones)
    • Growth of visceral organs, adipose and connective tissue, endocrine glands and skeletal muscle
  • Direct effects
    • Mediated by specific transmembrane receptors
    • 'Diabetogenic', opposes actions of insulin
    • Acts on adipocytes to increase lipolysis (increase free fatty acids)
    • Acts on skeletal muscle to increase glucose production
    • Decrease glucose uptake by tissues
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Actions of Growth Hormone

  • Indirect effects:
    • Mediated by insulin-like growth factors (IGFs), IGF-1
    • GH stimulates synthesis and release of IGF-1 from the liver (bone, fibroblasts, adipocytes, pituitary, kidney)
    • IGFs circulate tightly bound to plasma proteins to protect them from proteolysis
    • Bind to IGF receptors (skeletal muscle, liver, adipose tissue, chondrocytes in cartilage)
    • Increase protein production and cell proliferation
    • Levels rise during postnatal development, especially puberty, constant during adulthood
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Actions of Growth Hormone

  • IGF-1 acts on:
    • Bone
      • Proliferation and bone growth
    • Skeletal muscle
      • Differentiation and proliferation of myoblasts - muscle growth
    • Adipose tissue
      • Lipolysis
    • Liver
      • Increases glucose production and protein synthesis
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Posterior Pituitary Hormones and Their Targets

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Vasopressin/Antidiuretic Hormone

  • 9 amino acid peptide produced by the supraoptic nucleus and released from the posterior pituitary into the blood stream
  • Regulates body fluid volume
  • Main action - stimulates re-absorption of water from the distal convoluted tubules and collecting ducts --> decreased urine volume and increased body fluid
  • Prevents diuresis or fluid loss
  • Involves V2 receptors
  • Also has direct vasoconstrictor action --> increases blood pressure
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Control of Vasopressin Release

  • Controlled by plasma osmolarity (osmoreceptors) and blood volume/arterial pressure (baroreceptors)
  • Release also increased by other factors such as pain, fear, nausea, various drugs, general anaesthesia and neurotransmitters
  • Release inhibited by alcohol
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Control of Vasopressin Release

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