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This chapter discusses the endocrine system's regulatory mechanisms, focusing on the hypothalamic-pituitary axes and their feedback loops. It highlights the three main axes: Hypothalamic-Pituitary-Thyroid, Hypothalamic-Pituitary-Adrenal, and Hypothalamic-Pituitary-Gonadal. The chapter explains how hormone secretion is controlled through negative and positive feedback mechanisms, inhibitory control, and metabolic regulation. Additionally, it covers various hormone measurement methods, including immunoassays and bioassays, emphasizing the importance of accurate hormone level monitoring.
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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 (short and long loops) • Hypothalamic-Pituitary-Thyroid axis (HPT) • Hypothalamic-Pituitary-Adrenal axis (HPA) • Hypothalamic-Pituitary-Gonadal axis (HPG)
Control of Hormone Secretion • Basic or simple control • Negative feedback mechanism • Positive feedback mechanism • Inhibitory control • Metabolic control
Basic or simple control • Limited hormone made and/or stored • Full release on stimulation • Response is limited in magnitude or duration
Negative Feedback Loop • Most common control mechanism in endocrine system • Eg. thyroid releases T3 and T4 • Feedback to hypothalamus (and pituitary) limits releasing signal
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
Inhibitory Control • Hormones that are not released until a specific inhibitor is suppressed • Example: • Dopamine inhibition of prolactin release • Somatostatin inhibition of growth hormone
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
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
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
Measurement of Hormones • Hormones present in nanamolar to picomolar range • Very sensitive tests required
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
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
Summary • Axes and feedback loops • Control of hormone secretion • Measurements of hormones