endocrine part b

• Thyroid gland


  Butterfly-shaped gland in anterior neck on the trachea, just inferior to larynx
• Thyroid gland


  • Isthmus: median mass connecting two lateral lobes
  • Follicles: hollow sphere of epithelial follicular cells that produce glycoprotein thyroglobulin
  • Colloid: fluid of follicle lumen containing thyroglobulin plus iodine and is precursor to thyroid hormone
  • Parafollicular cells: produce hormone calcitonin
• Synthesis of thyroid hormone

  1. Thyroglobulin is synthesized and discharged into follicle lumen

  2. Iodide is trapped: iodide ions (I-) are actively taken into cell and released into lumen

  3. Iodide oxidized: electrons are removed, converting it to iodine (I2)

  4. Iodine is attached to tyrosine: mediated by peroxidase enzymes

  5. Monoiodotyrosine (MIT): formed if only one iodine attaches

  6. Diiodotyrosine (DIT): formed if two iodines attach

  7. Iodinated tyrosines link together to form T3 and T4

  8. Colloid is endocytosed by follicular cells

  9. Vesicle is then combined with a lysosome

  10. Lysosomal enzymes cleave T3 and T4 from thyroglobulin

  11. Hormones are secreted into bloodstream
• Thyroid hormone (TH)


  • T4 (thyroxine): major form that consists of two tyrosine molecules with four bound iodine atoms
  • T3 (triiodothyronine): form that has two tyrosines with three bound iodine atoms
  • Must be converted to T4 at tissue level
  • Both are iodine-containing amine hormones
• Thyroid hormone (TH)


  • Affects virtually every cell in body
  • Enters target cell and binds to intracellular receptors within nucleus
  • Triggers transcription of various metabolic genes
  • Increases basal metabolic rate and heat production (calorigenic effect)
  • Regulates tissue growth and development
  • Critical for normal skeletal and nervous system development and reproductive capabilities
  • Maintains blood pressure
  • Increases adrenergic receptors in blood vessels
• Transport and regulation of thyroid hormone

  1. T4 and T3 transported by thyroxine-binding globulins (TBGs)

  2. Both bind to target receptors, but T3 is 10 times more active than T4

  3. Peripheral tissues have enzyme needed to convert T4 to T3

  4. Falling TH levels stimulate release of thyroid-stimulating hormone (TSH)

  5. Rising TH levels provide negative feedback inhibition on TSH

  6. TSH can also be inhibited by GHIH, dopamine, and increased levels of cortisol and iodide

  7. Hypothalamic thyrotropin-releasing hormone (TRH) can overcome negative feedback during pregnancy or exposure to cold, especially in infants
• Calcitonin is produced by parafollicular (C) cells in response to high Ca2+ levels
• Calcitonin


  • Antagonist to parathyroid hormone (PTH)
  • No known physiological role in humans at normal physiological levels, but at higher-than-normal doses:
  • Inhibits osteoclast activity and prevents release of Ca2+ from bone matrix
  • Stimulates Ca2+ uptake and incorporation into bone matrix
• Parathyroid gland


  • Four to eight tiny yellow-brown glands embedded in posterior aspect of thyroid
  • Contain oxyphil cells (function not clear) and parathyroid cells that secrete parathyroid hormone (PTH), or parathormone
• Parathyroid hormone (PTH)


  • Most important hormone in Ca2+ homeostasis
  • Secreted in response to low blood levels of Ca2+
  • Inhibited by rising levels of Ca2+
  • Target organs are skeleton, kidneys, and intestine
• Effects of parathyroid hormone

  1. Stimulate osteoclasts to digest bone matrix and release Ca2+ to blood

  2. Enhances reabsorption of Ca2+ and secretion of phosphate (PO43-) by kidneys

  3. Promotes activation of vitamin D by kidneys, which leads to increased absorption of Ca2+ by intestinal mucosa
• Thyroid gland


  • Stimulate osteoclasts to digest bone matrix and release Ca2+ to blood
  • Enhances reabsorption of Ca2+ and secretion of phosphate (PO43-) by kidneys
  • Promotes activation of vitamin D by kidneys, which leads to increased absorption of Ca2+ by intestinal mucosa
• Effects of Parathyroid Hormone on Bone, the Kidneys, and the Intestine

  1. Hypocalcemia (low blood Ca2+)

  2. PTH release from parathyroid gland

  3. Osteoclast activity in bone causes Ca2+ and PO43- release into blood

  4. Ca2+ reabsorption in kidney tubule

  5. Activation of vitamin D by kidney

  6. Ca2+ absorption from food in small intestine
• Adrenal gland


  • Paired, pyramid-shaped organs atop kidneys
  • Also referred to as suprarenal glands
  • Structurally and functionally it is two glands in one
• Adrenal cortex


  Three layers of glandular tissue that synthesize and secrete several different hormones
• Adrenal medulla


  Nervous tissue that is part of sympathetic nervous system
• Corticosteroids produced by adrenal cortex

  • Mineralocorticoids
  • Glucocorticoids
  • Gonadocorticoids
• Mineralocorticoids


  Regulate electrolyte concentrations (primarily Na+ and K+) in ECF
• Aldosterone


  • Most potent mineralocorticoid
  • Stimulates Na+ reabsorption by kidneys
  • Results in increased blood volume and blood pressure
  • Stimulates K+ elimination by kidneys
• Renin-angiotensin-aldosterone mechanism


  1. Decreased blood pressure stimulates special cells in kidneys to release renin into blood

  2. Renin cleaves off part of plasma protein, angiotensinogen, that triggers enzyme cascade, resulting in conversion to angiotensin II

  3. Angiotensin II is a potent stimulator of aldosterone release
• Plasma concentration of K+

  • Increased K+ directly influences zona glomerulosa cells to release aldosterone
  • Increased K+ directly stimulates aldosterone release; low levels inhibit it
• ACTH


  Can cause small increases of aldosterone during periods of increased stress
• Atrial natriuretic peptide (ANP)


  • Secreted by heart in response to high blood pressure
  • Blocks renin and aldosterone secretion to decrease blood pressure
• Factors that regulate aldosterone secretion

  • Renin-angiotensin-aldosterone mechanism
  • Plasma concentration of K+
  • ACTH
  • Atrial natriuretic peptide
• Glucocorticoids


  • Influence metabolism of most cells and help us resist stressors
  • Keep blood glucose levels relatively constant
  • Maintain blood pressure by increasing action of vasoconstrictors
• Cortisol


  Only glucocorticoid in significant amounts in humans
• Regulation of cortisol secretion

  1. Cortisol is released in response to ACTH

  2. ACTH released in response to corticotropin-releasing hormone (CRH)

  3. CRH released in response to low cortisol levels

  4. Increased cortisol levels inhibit ACTH and CRH through negative feedback

  5. Cortisol secretion cycles are governed by patterns of eating and activity

  6. Acute stress interrupts cortisol rhythm

  7. CNS can override cortisol inhibition of ACTH and CRH, leading to more cortisol secretion
• Actions of cortisol


  • Causes increase in blood levels of glucose, fatty acids, and amino acids
  • Prime metabolic effect is gluconeogenesis, formation of glucose from fats and proteins
  • Encourages cells to use fatty acids for fuel so glucose is "saved" for brain
  • Enhances vasoconstriction, causes rise in blood pressure
• Excessive levels of glucocorticoids depress cartilage and bone formation, inhibit inflammation, depress immune system, and disrupt normal cardiovascular, neural, and gastrointestinal functions
• Gonadocorticoids (adrenal sex hormones)


  • Weak androgens (male sex hormones) converted to testosterone in tissue cells, some to estrogens
  • May contribute to onset of puberty and appearance of secondary sex characteristics, sex drive in women, and source of estrogens in postmenopausal women
• Adrenal medulla


  Medullary chromaffin cells synthesize catecholamines: epinephrine (80%) and norepinephrine (20%)
• Effects of catecholamines


  • Vasoconstriction
  • Increased heart rate
  • Increased blood glucose levels
  • Blood diverted to brain, heart, and skeletal muscle
• Epinephrine vs Norepinephrine


  • Epinephrine is more a stimulator of metabolic activities
  • Norepinephrine has more of an influence on peripheral vasoconstriction and blood pressure
• Short-term stress response


  1. Stressors trigger action potentials in hypothalamus that activate sympathetic nervous system

  2. Adrenal medulla secretes epinephrine and norepinephrine

  3. Catecholamines reinforce other sympathetic responses to ready the body for exertion ("fight or flight")

  4. Cardiovascular, respiratory, and metabolic effects
• Long-term stress response


  1. Stressors cause hypothalamus to release corticotropin-releasing hormone (CRH)

  2. CRH stimulates anterior pituitary to release adrenocorticotropic hormone (ACTH)

  3. ACTH stimulates adrenal cortex to synthesize and release glucocorticoids (and some mineralocorticoids)

  4. Glucocorticoids have metabolic effects to provide fuel and maintain blood pressure

  5. Prolonged stress response can be detrimental, leading to high blood pressure, muscle loss, altered immune function, and other problems
• ACTH


  Adrenocorticotropic hormone
• ACTH action


  1. ACTH travels in blood to the adrenal cortex

  2. Adrenal cortex synthesizes and releases glucocorticoids (e.g. cortisol) and some mineralocorticoids (e.g. aldosterone)
• Adrenal cortex hormones


  • Mineralocorticoids
  • Glucocorticoids
• Mineralocorticoids


  • Renal effects
• Glucocorticoids


  • Metabolic effects
  • Protein breakdown
  • Blood amino acids (for new protein synthesis if required for emergency)
  • Blood glucose (fuel for brain)
  • Blood fatty acids (fuel for muscles)
  • Fat breakdown