E3

• Pituitary gland

  Master gland, conducts the rest
• Pituitary gland

  • Combo of neurones and other cells
  • It has an extension from the brainstem
  • Nuclei= collection of cells
• Hypothalamus

  A collection of brain nuclei or centres which have important control and integrative functions
• Hypothalamus

  • Important for homeostasis and primitive functions
  • It controls autonomic function via brainstem autonomic centres
  • It controls endocrine function via the pituitary gland
• What the hypothalamus responds to

  • Environmental factors
  • Neural signals
  • Hormone
• Environmental factors the hypothalamus responds to

  • Light (circadian rhythm)
  • Stress e.g. noise, fear
• Neural signals the hypothalamus responds to

  • Visceral afferents from the intestines, heart, liver, stomach
  • Mediated by glutamate, serotonin, Ach, histamine, GABA, dopamine
• Hormone the hypothalamus responds to

  • Negative feedback
• Hypothalamic hormones

  • TRH- a tripeptide- TSH, PRL, FSH
  • GnRH- decapeptide- LH, FSH
  • GHRH- 44aa- GH
  • Somatostatin- 14aa- GH
  • CRH- 41aa- ACTH
  • Dopamine- monoamine- PRL
• Properties of hypothalamic hormones

  • Small peptides with short half life
  • Release is pulsatile, inducing rapid effects on the release of cognate anterior pituitary hormone
  • Can be used clinically in acute challenge experiments to check pituitary function
• Pituitary gland

  Anterior (adenohypophysis) and posterior (neurohypophysis) lobes
• Anterior pituitary

  • Hormones regulated by secreted hypothalamic factors
• Posterior pituitary

  • Hormones synthesised in hypothalamus and transported via neuronal projections
  • Structurally continuous with the hypothalamus of the brain- attached by the hypophyseal or pituitary, stalk
• Anterior pituitary hormones

  • Thyrotroph (TSH)- thyroid hormone regulation
  • Corticotroph (ACTH)- regulation of adrenal cortex
  • Gonadotroph (LH/FSH)- reproductive control
  • Somatotroph (GH)- growth
  • Lactotroph (PRL)- milk production
• Posterior pituitary hormones

  • ADH (vasopressin)- water regulation
  • Neurophysins- important in ADH synthesis
  • Oxytocin- birth, breast milk expression
• Hypothalamus and pituitary central to many hormonal axes
• Arginine vasopressin AKA Antidiuretic hormone (ADH)

  Nonapeptide- secreted from posterior pituitary
• ADH

  • Vasopressin- synthesised and packaged with a carrier protein 'neurophysin' in secretory granules in the magnocellular neurones of the paraventricular and supraoptic nuclei
  • The granules move down to ends of fibres
  • Both are released upon stimulation of nerves
• ADH secretion and plasma osmolarity

  • More ADH to retain water- when dehydrated
  • As plasma concentration of ADH increases, Plasma osmolarity increases too
• ADH action

  • ADH acts on collecting ducts of kidney
  • Collecting ducts intrinsically impermeable to water
  • ADH stimulates the production of water channels and their incorporation into the walls of the collecting ducts
  • This allows reabsorption of 'free' water from tubular fluid
  • Can convert very dilute urine to a very concentrated urine
• ADH excess

  • Due to damage to head, secreting tumours
  • Syndrome of inappropriate ADH secretion (SIADH)
  • Water retention (low serum sodium concentration) leads to highly concentrated urine
• ADH deficiency

  Excess water retention
• Diabetes Insipidus

  • ADH needed for H20 absorption in the renal collecting ducts
  • ADH controls serum osmolarity
  • During water deprivation, ADH levels should increase to allow water reabsorption, and increase urine concentration and decrease urine volume
  • But if posterior pituitary damaged- ADH may be reduced so no concentrated urine
  • Secondary to generalised pituitary disease or isolated/idiopathic
  • Result: Polyuria (excess urine production)- more than 3 litres per day and polydipsia (excess drinking)
  • Hypernatremia and increased serum osmolality result
  • Diagnosed by having dilute urine in the context of concentrated plasma
• Oxytocin

  • Stimulates contraction of smooth muscle (Myoepithelial cells) of breast and uterus
  • Can be given to induce labour
  • Roles in: milk ejection reflex and parturition (birth)
  • Neuro-endocrine reflexes- neural signals make neuro-endocrine cells secrete hormones from the neural axon terminals into the blood
• Cell types in anterior pituitary

  • Corticotrophs- functional tumours= Cushing's
  • Somatotroph- functional tumours= acromegaly
  • Gonadotrophs- nonfunctioning tumours are common
  • Thyrotrophs- functional tumours of thyrotrophs and gonadotrophs rare
  • Lactotrophs- functional tumours= prolactinoma
• Anterior pituitary hormones

  • Tropic hormones target other endocrine glands
  • Glycoproteins have alpha and beta subunit
  • Produced by 5 types of secretory cells in the anterior pituitary- thyrotropes, gonadotropes, corticotropes, somatotropes, lactotropes
• Anterior pituitary glycoprotein hormones

  • Thyroid stimulating hormone (TSH)
  • Follicle stimulating hormone (FSH)
  • Luteinising hormone (LH)
• Anterior pituitary protein and polypeptide hormones

  • Adrenocorticotropic hormone (ACTH)
  • Growth hormone (GH)
  • Prolactin
• Protein hormones of the anterior pituitary

  • Single chain: Prolactin- 199AA, Growth hormone- 191AA, 22kDa
  • Two chain glycoproteins: TSH, LH, FSH- 28kDa
• TSH

  • Aka thyrotropin and thyrotrophin
  • Made in thyrotrophs of the anterior pituitary (about 5% of the cells) in response to pulsatile TRH release from the hypothalamus
• Hypothalamic-pituitary- thyroid axis

  • 2 related molecules exert negative feedback
  • Positive TRH input from the hypothalamus
  • Prohormone (T4) to hormone (T3) in target tissue
• Thyrotroph problems

  • Pituitary failure- secondary hypothyroidism
  • Pituitary tumour (extremely rare)- secondary hyperthyroidism
• Gonadotrophins

  • LH and FSH
  • Made in gonadotrophs of AP (5-10% cells) in response to GnRH
  • 60% of these secrete both, 18% secrete only LH, 22% secrete only FSH
• Effects and mechanisms of action of LH and FSH

  • Regulate testosterone biosynthesis and spermatogenesis in the testes
  • Regulate the menstrual cycle and fertility in the ovary
  • Both act through cell membrane receptors coupled to Gs proteins
  • Result in elevations in cAMP and activation of protein kinase A
  • Pulsatile secretion essential for actions
• Adrenocorticotrophic hormone (ACTH) aka Adrenocorticotrophin

  • Polypeptide of 39aa, residues 1-24 conserved and used as synthetic analogue
  • Synthesized in corticotrophs of the anterior pituitary- about 10% of cells
  • Can be synthesised from Pro-opiomelanocortin (POMC)
• Hypothalamic-pituitary-adrenal axis

  • Positive input from hypothalamus
  • Secondary messenger cAMP
  • A single molecule can exert negative feedback
  • Involves corticotrophin releasing hormone (CRH) and ACTH
• Effects of ACTH

  • ACTH stimulates G-protein receptor coupled to cAMP
  • This stimulates the enzymes that convert cholesterol to cortisol or sex steroid precursors
  • Like PRL and GH, ACTH rises with stress, e.g. hypoglycaemia. This is used to clinically test corticotroph function following insulin challenge
• Prolactin

  • Made in lactotrophs which comprise 15-20% of cells
  • This percentage increases during pregnancy due to oestrogen
• Prolactin regulation

  • Major control is exerted by dopamine, which as a negative influence
  • Somatostatin – also has a negative effect
  • Prolactin release is stimulated by vasoactive intestinal peptide
• Effects of prolactin

  • Stimulates mammary gland development: DNA synthesis, Epithelial cell proliferation, Synthesis of casein and lactalbumin, Synthesis of lactose, Synthesis of free fatty acids
  • Maintains lactation: Synergized by glucocorticoids, Inhibited by oestrogen and progesterone
  • Other effects: lymphocytes: regulation e.g. Nb2 cells, kidney and anion, choroid plexus (osmoregulation), ovary: maintenance or regression of corpus luteum and steroid production, testis: steroid production, liver: RNA synthesis