Endocrine System and Muscle Physiology: Hormones, Contraction & More

Endocrine System and Muscle Physiology

Motor Neuron Axon Terminal

  1. Action potential reaches axon terminal of motor neuron.
  2. Voltage-gated Ca2+ channels open, allowing Ca2+ to enter the motor neuron.
  3. Vesicles fuse with axon terminal membrane, releasing acetylcholine (ACh) into the synapse (always excitatory between motor neuron and muscle cell).
  4. ACh diffuses to the skeletal muscle cell membrane and binds to nicotinic acetylcholine receptors (nAChR).
  5. nAChR are activated, allowing ions to enter the muscle cell, causing an action potential.
  6. Action potential travels along the muscle cell membrane, including along the T-tubules.
  7. Action potential enters dihydropyridine receptors (DHPRs) in the muscle cell membrane, which are connected to ryanodine receptor channels in the sarcoplasmic reticulum membrane.
  8. Ryanodine receptor channels open, allowing Ca2+ to be released into the cytosol.
  9. Ca2+ binds to troponin, changing its shape and causing tropomyosin to move, exposing the binding sites on actin.
  10. Ca2+ pumps in the sarcoplasmic reticulum membrane pump Ca2+ out of the cytosol and back into the sarcoplasmic reticulum (if the Ca2+ concentration in the cytosol drops low enough, Ca2+ will disassociate from troponin and stop cross-bridge cycling).

Anterior Pituitary Hormones

  • FSH & LH: Stimulate gonads for the release of estrogen, testosterone, and germ cell development.
  • TSH: Stimulates the thyroid to produce T4 and subsequently T3.
  • GH: Stimulates the liver and other organs and tissues to secrete growth factors, synthesize proteins, and metabolize carbohydrates and fats; stimulates IGF-1 in skeletal muscle and liver.
  • ACTH: Stimulates the adrenal cortex to produce cortisol.
  • Prolactin: Stimulates breast development and milk production (release controlled by hypothalamic nuclei; hormones from this are called hypophysiotropic hormones; released into HHPS and delivered to the anterior pituitary).

Amine Hormones

Thyroid and catecholamines are also called monoamine hormones. A class of hormones, each composed of a single amino acid that has been modified into a related molecule, such as melatonin or epinephrine.

Thyroid Hormones

Function: Metabolic rate, growth, brain development
Source: Amino acid tyrosine
Forms: T3 (active form), T4 (inactive storage form)

Catecholamines

Source: Amino acid tyrosine

Peptide Hormones

Coded in the genome.

Protein Hormones

Can evolve as coded in the genome, stored in vesicles because making them is time-consuming.

Steroid Hormones

Primarily produced in the adrenal cortex and gonads, formed through biochemical transformations of cholesterol.

Adrenal Cortex Hormones

  • Aldosterone: Salt balance in kidneys
  • Cortisol/Corticosterone: Glucose metabolism
  • DHEA/Androgens: Sexual development & puberty

Gonadal Hormones

  • Estradiol (Estrogen): Growth, sexual development, and puberty
  • Testosterone (Androgen): Growth, sexual development, and puberty

Muscle Proteins

Tropomyosin: A protein of muscle that forms a complex with troponin, regulating the interaction of actin and myosin in muscular contraction. Regulatory protein of thin filaments, blocks myosin binding sites.

Troponin: A smaller calcium-binding protein attached to tropomyosin; holds tropomyosin in place.

Cross-Bridge Cycle

I: Resting State

Myosin heads energized, tropomyosin covers the binding site on actin, troponin holds tropomyosin in place.

I: Cross-Bridge Binding

Ca2+ binds to troponin, troponin changes shape, tropomyosin moves and uncovers the binding site on actin, myosin head binds to actin forming a cross-bridge.

II: Power Stroke

ADP and Pi disassociate from the myosin head, myosin head (still bound to actin) causing actin to move.

II: Cross-Bridge Release

ATP binds to myosin heads causing them to let go of actin, ATP hydrolyzed into ADP and Pi, myosin heads shift back to resting/energized position (if Ca2+ high: another cross-bridge cycle, if Ca2+ low: resting state/relaxed muscle).

Muscle Length and Force Monitoring Systems

Muscle Spindles: Sense length change:
a) The stretched muscle spindle generates a burst of action potentials as the muscle is lengthened.
b) The shortened muscle spindle produces fewer action potentials.

Golgi Tendon Organ: Senses muscle force; the more force a muscle produces, the more it stretches the tendon it is attached to, stretch in tendon fibers stretches the nerve cell membrane, causing depolarization by mechanical stretch-induced opening.

Bone Growth Control

  • Growth Hormone: Produced by the anterior pituitary (mediated through IGF-1, produced in the liver).
  • PTH: Controls bone resorption and calcium balance.

Cortisol Effects on Metabolism

Promotes new glucose (protein catabolism into amino acids and liver conversion of amino acids to glucose), opposes insulin, increases appetite, mobilizes fat (into fatty acids and glycerol which can then enter the Krebs Cycle).

Brody Disease

Exercise-induced muscle stiffness, delayed muscle relaxation after repetitive contraction, strength preserved, creatine kinase levels were normal or elevated, reduction or absence of protein crucial for muscle relaxation, hyperthermia.

Diabetes Type I and II

T1DM is characterized by the destruction of beta cells in the pancreas, typically secondary to an autoimmune process. The result is the absolute destruction of beta cells, and consequently, insulin is absent or extremely low. T2DM involves a more insidious onset where an imbalance between insulin levels and insulin sensitivity causes a functional deficit of insulin. Insulin resistance is multifactorial but commonly develops from obesity and aging. HbA1c monitoring, polydipsia (excessive thirst), polyuria (excessive urination).

Primary Hypothyroidism

Condition where the thyroid gland does not produce enough thyroid hormones. Iodine deficiency, symptoms such as fatigue, weight gain, and cold intolerance. TSH testing and levothyroxine therapy.

Key Terms

Aldosterone: A hormone that helps regulate the body’s water and salt balance, and blood pressure.

Creatine Kinase: An enzyme that helps produce energy in cells and is found in the heart, skeletal muscles, and brain.

Intrafusal Muscle Fibers: Small, sensory receptors that are part of the muscle spindle and are responsible for providing information about muscle tension to the CNS.

nAChR: Responsible for opening a ligand-gated Na+/K+ channel in the muscle membrane when the proper ligand binds to it.

Neuromuscular Junction and Contraction

How does the neural impulse at the NMJ result in contraction?
1. Depolarizing current carried through t-tubules.
2. Release of Ca2+ stores from the sarcoplasmic reticulum.
3. Increase of intracellular [Ca2+].
4. Cross-bridge cycling can now occur.

Hypophysiotropic Hormones

Hormones released from hypothalamic nuclei are called hypophysiotropic hormones:

  • Corticotropin-releasing hormone (CRH): Stimulates ACTH release.
  • Thyrotropin-releasing hormone (TRH): Stimulates TSH release.
  • Growth hormone-releasing hormone (GHRH): Stimulates GH release.
  • Somatostatin (SST): Inhibits GH release.
  • Gonadotropin-releasing hormone (GnRH): Stimulates LH & FSH release.
  • Dopamine: Inhibits prolactin secretion.

Z

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