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Chapter 2

Chapter 2. Endocrine system control axes and feedback loops Hormone measurement methods, normal range, fluctuations. Hypothalamic-Pituitary Axes. Three main axes involving hypothalamus and pituitary control much of endocrine system - operate by negative feedback

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Chapter 2

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  1. Chapter 2 • Endocrine system control • axes and feedback loops • Hormone measurement • methods, normal range, fluctuations

  2. Hypothalamic-Pituitary Axes • Three main axes involving hypothalamus and pituitary control much of endocrine system - operate by negative feedback (short and long loops) • Hypothalamic-Pituitary-Thyroid axis (HPT) • Hypothalamic-Pituitary-Adrenal axis (HPA) • Hypothalamic-Pituitary-Gonadal axis (HPG)

  3. Hypo – Pit-Thyroid Axis

  4. Hypo-Pit-Gonadal Axes

  5. Control of Hormone Secretion • Basic or simple control • Negative feedback mechanism • Positive feedback mechanism • Inhibitory control • Metabolic control

  6. Basic or simple control • Limited hormone made and/or stored • Full release on stimulation • Response is limited in magnitude or duration

  7. Negative Feedback Loop • Most common control mechanism in endocrine system • Eg. thyroid releases T3 and T4 • Feedback to hypothalamus (and pituitary) limits releasing signal

  8. Positive Feedback Control • Less common mechanism • Used when signal amplification is needed • Eg. Oxytocin (made in hypothalamus and released by posterior pituitary) during parturition and suckling • E.g. Mid-cycle LH/FSH surge induced by high levels of estrogen

  9. Inhibitory Control • Hormones that are not released until a specific inhibitor is suppressed • Example: • Dopamine inhibition of prolactin release • Somatostatin inhibition of growth hormone

  10. Metabolic Control • Activation of bioactive hormone requires modification (cleavage, de-iodination, reduction) • May occur in target tissue • Eg. 5-alpha reductase converts testosterone (T) to bioactive dihydrotestosterone (DHT) • Aromatase converts androgen to estrogen

  11. Endocrine Rhythms • Hormone levels may fluctuate in response to external stimuli (food, light, activity) • Circadian and longer rhythms also exist • E.g., pulsatile secretion of pituitary growth hormone

  12. Fluctuations • Changes in hormone levels occur normally throughout day (and night) • Accurate measures may require multiple sampling over time • Peripheral blood levels are only one measure; local concentrations may be higher and more relevant

  13. Measurement of Hormones • Hormones present in nanamolar to picomolar range • Very sensitive tests required

  14. Immunoassays • Radioimmunoassay (RIA)– Pure radiolabelled hormone (H*) binds to antibody and Unlabelled hormone (H) from bio-fluid competes for binding and displaces H* • Non-radioactive Enzyme-Linked ImmunoSorbent Assay (ELISA) – Immobilized 1st antibody binds hormone that in turn captures an enzyme-tagged 2nd antibody. • Sensitive, quantiative

  15. Other Hormone Assays • Radioreceptor assays (RRA)s use hormone receptors instead of antibodies • Bio-assays use target cell outcomes to measure biological activity of hormone sample (or biological fluid) • Cells in culture may respond by expressing a known gene product • New science of detecting “endocrine disruptors” in environmental materials

  16. Summary • Axes and feedback loops • Control of hormone secretion • Measurements of hormones

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