Midterms Doc Calban

• Endocrine system


  Made up of various endocrine glands that each secrete hormones into bloodstream

  
• Hormones


  Chemical messengers released into the blood
• Hormone target


  Any cell in which the hormone (ligand) binds to its receptor, whether or not a biochemical or physiologic response has yet been determined
• Pituitary gland

  • Anterior pituitary derived from oral ectoderm (Rathke's Pouch)
  • Posterior pituitary derived from neural ectoderm (neural hypothalamus)
  • Anterior pituitary has basophilic and acidophilic cells
  • Posterior pituitary stores and secretes prolactin, oxytocin, and vasopressin
• Anterior pituitary hormones


  • Growth hormone (somatotropin)
  • Thyroid stimulating hormone (TSH)
  • Adrenocorticotropic hormone (ACTH)
  • Follicle stimulating hormone (FSH)
  • Luteinizing hormone (LH)
  • Prolactin
• Steroid hormones


  Hydrophobic (non-polar), made from cholesterol, from adrenal gland, ovaries, testes

  
• Non-steroid hormones


  Amino acids, peptides, thyroid hormones, epinephrine/norepinephrine, insulin, glucagon

  
• General classification of hormones


  • Steroids, thyroid hormones, vitamin D & A
  • Polypeptides, proteins, glycoproteins, catecholamines

  
• Protein hormones


  Water soluble, non-steroids, bind to cell membrane receptors, activate enzymes via 2nd messengers
• Lipid hormones


  Lipid soluble, steroids, bind to intracellular receptors, regulate gene transcription
• Mechanisms of hormone action


  • Bind to intracellular receptors (steroids)
  • Bind to cell surface receptors (peptides)
  • cAMP
  • cGMP
  • Calcium/phosphatidylinositol
  • Kinase/phosphatase cascade
• Determinants of hormone concentration at target cell

  • Rate of synthesis and secretion
  • Proximity of target cell to hormone source
  • Affinity of hormone with plasma transport proteins
  • Conversion of inactive to active forms
  • Rate of hormone clearance

  
• Determinants of target cell response


  • Number, activity, and occupancy of receptors
  • Metabolism of hormone in target cell
  • Presence of other factors in cell
  • Up/down regulation of receptors
  • Post-receptor desensitization
• Regulatory mechanics


  Binding should be specific, saturable, and within expected biological response range
• Hormone regulation


  • Negative feedback
  • Positive feedback
  • Upregulation
  • Downregulation
• Diversity of hormone synthesis

  • Discrete organs designed solely for hormone synthesis
  • Organs with two distinct functions (e.g. ovaries, testes)
  • Specialized cells within other organs
• Diversity of hormone synthesis and modification


  • Synthesized in final form and secreted immediately
  • Synthesized in final form and stored
  • Synthesized as precursor and processed before secretion
  • Converted to active form in peripheral tissues

  
• Aldosterone


  Under tonic control by ACTH but separately regulated by RAAS and K+, increases Na reabsorption and K secretion in kidneys and colon, increases transport of epithelial Na channels to cell membrane

  
• Cortisol


  • Stimulates gluconeogenesis
  • increases protein utilization
  • decreases glucose utilization and insulin sensitivity of adipose tissue
  • decreases cellular proteins (except liver)
  • increases blood amino acids
  • increases liver and plasma proteins
• Aldosterone has the greatest effects on Na excretion, while ADH has the greatest effects on plasma osmolality

  
• Hyperkalemia


  Increases aldosterone secretion to restore K to normal

  
• Effects of aldosterone


  1. Na reabsorption in kidneys, sweat glands, salivary glands, and colon

  2. K secretion in kidneys and colon

  3. H secretion in kidneys (triggered by hyperkalemia)

  
• Aldosterone


  Increases transport of epithelial Na channels from cytoplasm to cell membrane
• Greatest effects


  • Aldosterone on Na excretion
  • ADH on plasma osmolality

  
• Cortisol


  • Essential response to stress
  • Oscillates with circadian rhythm
  • Highest levels: before waking up (~8AM)
  • Lowest levels: in the evening (~midnight)
  • Rise sharply during sleep
  • Peak soon after awakening
  • Sink to a low level 12 hours later
• Cortisol


  Anti-inflammatory effects
• Addison's disease


  • Low aldosterone: Hypotension, Hyperkalemia, Metabolic acidosis
  • Low cortisol: Hypoglycemia, Anorexia, Weight loss, Nausea/vomiting, Weakness
  • Low weak androgens: Decreased pubic and axillary hair (F)
  • Hyperpigmentation

  
• Cushing's syndrome


  • Hypertension, Hyperglycemia, Muscle wasting, Central obesity, Round face, Supraclavicular fat, Buffalo hump, Osteoporosis, Striae, Virilization, Menstrual d/o
• Conn's syndrome


  • Hypertension, Hypokalemia, Metabolic alkalosis, Decreased Renin

  
• POMC has MSH which causes stimulation of melanocytes to secrete melanin
• Adrenal gland zones


  • Glomerulosa: Aldosterone
  • Fasciculata: Cortisol
  • Reticularis: Androstenedione, Dehydro-epi-androsterone (DHEA)

  
• Adrenal medulla


  • Epinephrine: 80%
  • Norepinephrine: 20%
• Half-life


  • Epinephrine = 2 mins
  • Norepinephrine = 2 mins
  • Renin = 15 mins
  • Aldosterone = 20 mins
  • Corticosterone = 60-90 mins
  • DHEA = 7-22 hrs

  
• 21-beta hydroxylase deficiency


  • Virilization in women, Pseudoprecocious puberty in men, Early acceleration of linear growth, Symptoms of GC and MC deficiency, Lack of pubic and axillary hair in women

  
• 17-alpha hydroxylase deficiency


  • Symptoms of GC and MC excess

  
• Testicular steroidogenesis


  • Cholesterol is the immediate precursor of gonadal steroids
  • Rate-limiting step is delivery of cholesterol to the inner membrane of the mitochondria by the transport protein StAR
• Testosterone


  • Differentiation of epididymis, vas deferens, and seminal vesicles
  • Descent of testes
  • Increases bone and muscle mass
  • Increases BMR
  • Pubertal growth spurt
  • Epiphyseal closure
  • Growth of penis and seminal vesicles
  • Deepening of voice
  • Spermatogenesis
  • Negative feedback on APG
  • Libido
• Dihydrotestosterone (DHT)


  • Formed from testosterone
  • Most significant metabolic product of testosterone
  • Active form of testosterone in prostate, external genitalia, and some areas of skin
  • Testosterone is a prohormone since it is converted into a much more potent compound (DHT) and most conversion occurs outside testes
• Dihydrotestosterone (DHT)


  • Differentiation of penis, scrotum, and prostate
  • Male hair pattern
  • Male pattern baldness
  • Sebaceous gland activity
  • Growth of prostate
• Ovarian estrogens


  • Estradiol = main form during reproductive years
  • Estriol = during pregnancy
  • Estrone = during post-menopausal years