Anatomy and physiology

• The hypothalamic-pituitary-thyroid axis consists of the hypothalamus, the pituitary gland and they thyroid gland
• Hypothalamic-Pituitary-Thyroid Axis Regulation:

  • The hypothalamus produces thyrotrophin-releasing hormone (TRH)
  • TRH binds to TRH receptors on thyrotropic cell membranes in the anterior pituitary, stimulating the production of thyroid-stimulating hormone (TSH)
  • TSH enters the blood and binds to receptors on follicular cells of the thyroid gland, stimulating the production of thyroid hormones T3 and T4
• Regulation of thyroid hormones is via negative feedback - high levels of T3 and T4 inhibit TRH production by the hypothalamus and TSH from the anterior pituitary
• The thyroid gland is located in the anterior neck and spans the C5-T1 vertebrae. It consists of two lobes (left and right), which are connected by a central isthmus anteriorly – this produces a butterfly-shape appearance
• The thyroid gland is supplied by superior and inferior thyroid arteries and drained via superior, middle and inferior thyroid veins
• The actions of T3 and T4 are widespread. Some important functions include:

  • Metabolic – increasing basal metabolic rate and promoting catabolism e.g. lipolysis, glycogenolysis, glycolysis and proteolysis
  • Nervous system – important for speed of reflexes and mental activity
  • Cardiovascular system – increases synthesis of cardiac muscle protein, increases cardiac output
  • Bone – increases bone mineralisation
• Endocrine function of the pancreas:

  • Islets of langerhans
  • Alpha cells - secretion of glucagon
  • Beta cells - secretion of insulin and amylin
• Glucagon:

  • Increases blood glucose levels
  • Stimulated by adrenaline and noradrenaline
  • Single chain polypeptide
  • Binds to G protein coupled receptor
  • Increased glycogenolysis and gluconeogenesis in the liver
  • Increased ketogenesis in the liver - break down of fatty acids and amino acids
• Insulin:

  • Reduces blood sugar levels
  • 2 polypeptide chains - A and B - connected by 2 disulphide bridges
  • Insulin causes increased GLUT-4 expression on the surface of cells - increased glucose uptake
  • Increased glycogenesis in the muscle and liver
  • Increased glycolysis in the liver and adipose tissue
  • Decreased ketogenesis
• The hypothalamus has a close relationship with the pituitary gland - this is known as the hypothalamic-adenohypophyseal axis

  Hormones are released from the median eminence of the hypothalamus into the hypophyseal portal system, where they travel to the anterior pituitary
• There are two posterior pituitary hormones:

  • Oxytocin
  • Antidiuretic hormone
• Osmoreceptors in the hypothalamus regulate ADH release by detecting and responding to changes in plasma osmotic pressure (concentration of the blood)

  ADH acts on the kidney's collecting ducts to increase water reabsorption
• The hypothalamic-pituitary-adrenal axis:

  1. stress, infection or blood loss can stimulate the hypothalamus to secrete corticotropin-releasing hormone (CRH)
  2. CRH acts on corticotropes in the anterior pituitary, which then releases ACTH - corticotropin
  3. ACTH stimulates the adrenal cortex to release cortisol
  4. increased serum cortisol levels inhibit the production of CRH and ACTH via negative feedback
• Cortisol is released in response to low blood sugars - promotes gluconeogenesis
• Hormones released from the anterior pituitary gland:

  • Adrenocorticotropic hormone (ACTH) - in response to CRH
  • Thyroid stimulating hormone (TSH) - in response to thyroid releasing hormone
  • Growth hormone (GH)
  • Follicle stimulating hormone (FSH) and Luteinising hormone (LH)
  • Prolactin
• Adrenal glands are above each kidney

  • Adrenal cortex = produce cortisol and aldosterone
  • Adrenal medulla = produce adrenaline and noradrenaline (under the direct control of the hypothalamus)
• Aldosterone is a mineralocorticoid (steroid) hormone whose main function is to increase blood volume - promotes the reabsorption of sodium and water, whilst excreting potassium
• The release of aldosterone from the adrenal glands is regulated via the RAAS system - angiotensin II triggers the synthesis and release of aldosterone from the adrenal cortex

  Aldosterone release is also released in response to high ACTH or potassium
• Endocrine function of the kidneys:

  • Renin secretion from the renal juxtaglomerular cells leads to the production of angiotensin II - stimulates aldosterone release from the adrenal cortex
  • Erythropoietin production - released in response to hypoxia and stimulates haemoglobin production
  • Produces the biologically active form of vitamin D
• Regulation of growth hormone:

  • Hypothalamus secretes growth hormone releasing-hormone
  • Anterior pituitary releases growth hormone - also called somatotropin
• Growth hormone disorders:

  • In children, a deficiency of GH could result in short stature due to slow bone and muscle maturation and delayed puberty
  • Growth hormone excess in adults = acromegaly - usually caused by a pituitary tumour secreting GH
  • Growth hormone excess in children before the bony epiphyses have fused results in gigantism
• ADH is also called vasopressin

  It acts on the distal convoluted tubules of the kidneys

  Binding of ADH causes aquaporin-2 channels to move into the membrane and allow water to be reabsorbed out of the collecting ducts and back into the bloodstream
• Insulin causes the muscle and liver cells to absorb glucose from the blood and store it as glycogen - glycogenesis