Mechanisms of Hormone Action

Homeostasis - maintains body's internal environment within a set of normal parameters

• Intrinsic regulation - cell/tissue/organ adjusts itself to environmental change
• Extrinsic regulation - nervous or endocrine systems adjust cell/tissue/organ to environmental change and coordinate other systems, requires long distance communication
  • Nervous system - rapid, short-term, specific effect, limited targets; gap or synaptic
  • Endocrine system - slower, long-term, broad effect, more targets; chemical messengers

Exocrine glands - glandular cells secrete products into ducts

Endocrine glands - glandular cells secrete products into ECF around gland

Neuroendocrine - secreted by neuron endings into ECF

Hormones

• Chemical messengers produced by endocrine glands which are usually carried in the circulatory system or interstitial fluid to target cells
• Released continuously or in short bursts, amount and frequency can vary
• Circulating hormones are transported by blood in solution or attached to plasma proteins
• Local hormones remain in interstitial fluid and act on nearby cells
  • Autocrines act on the cells that secrete them
  • Paracrines act on neighboring cells, local hormones
• Produce slower response than nervous system but longer lasting effects
• Inactivated by liver & excreted by kidneys
• Function:
  1. stimulate synthesis of enzymes or structural proteins
  2. change rate of synthesis
  3. inactivate or activate existing enzymes or protein channels
• Endocrine reflexes respond to ECF changes, hormonal levels, neural stimuli; usually controlled by negative feedback
  • Reflex arc: stimulus, hormone release, ECF, target cell receptors, cellular response

Hormone types:

• Steroids - lipid with cholesterol center, varies based on side-groups, travel bound
  • Ex. sex hormones, corticosteroids, calcitriol, aldosterone
• Eicosanoids - derived from 20-C arachidonic acid
  • Local hormones produced in most cells, rapid breakdown
  • Ex. prostaglandins - huge variety of effects, work in small doses, mimic some other hormone effects, decrease gastric secretion, induce abortion & labor
  • Ex. leukotrienes - released by WBC, coordinate tissue response to injury or disease
• Amines - simplest form, derived from tyrosine or tryptophan
  • Ex. TH, dopamine, epinephrine, melatonin
• Peptides - 9-200 amino acids, greatest variety
  • Ex. all hypothalamic, anterior pituitary, digestive hormones
• Nitric oxide (NO) - acts as hormone and neurotransmitter

Target cells

Specific cells are affected by hormone and respond in unique fashion

• Cells have specific receptors on membrane or in cell that respond to hormone
• Can have receptors for several different hormones
• Number of active receptors can change
  • Down-regulation - number of receptors decreases & target is less sensitive
  • Up-regulation - number increases & target is more sensitive

Mechanisms of hormone action

Allows for amplification of effect

1. Lipid soluble hormones - ex. steroids, NO, TH
   1. hormone diffuses through lipid bilayer into cytoplasm
   2. binds to cytoplasmic or nuclear receptor
   3. activated receptor binds to DNA & turns genes on or off
   4. if on, increases transcription of specific RNA
   5. new enzymes alter cell activity
2. Water soluble hormones - ex. proteins, amines, eicosanoids
   1. hormone binds to membrane outer surface receptor = 1^st messenger
   2. binding activates G- protein in the membrane that activates or inhibits adenylate cyclase on the inner surface of membrane
   3. adenylate cyclase converts ATP to cAMP = 2^nd messenger
   4. Ca⁺², cGMP, IP₃, & DAG are also 2^nd messenger types
   5. cAMP activates protein kinases that phosphorylate cellular enzymes, changing their configuration & either activating or inactivating them
   6. phosphodiesterase inactivates cAMP

   or

   1. hormone binds to membrane outer surface receptor = 1^st messenger
   2. binding activates G- protein in the membrane that activates phospholipase C (PLC)
   3. PLC triggers IP₃ which releases intracellular Ca⁺²
   4. PLC triggers DAG (diacylglycerol), which combined with Ca⁺² activates PKC (protein kinase C)
   5. PKC phosphorylates calcium channel proteins allowing extracellular Ca to enter
   6. Ca plus calmodulin activates specific enzymes

Target cells sensitive to several hormones may show interactive effects.

1. Permissive effects - first hormone enhances the effect of a later hormone action
   1. ex. estrogen up-regulates progesterone receptors in uterus
   2. ex. TH increases effect of epinephrine on breakdown of triglycerides in adipocytes
2. Integrative effects - hormones produce different by complementary effects on different tissues
   1. ex. PTH and calcitriol increase ECF calcium
3. Synergistic effects - two hormones acting together have a greater effect than the sum of the effects of each hormone acting independently
   1. ex. both FSH and estrogen necessary for normal oocyte development
   2. ex. FSH and testosterone together produce more sperm than alone
4. Antagonistic effects - one hormone opposes the action of the other hormone, net effect
   1. ex. insulin and glucagon