Hydrophobic Hormone Signaling and Receptors
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Questions and Answers

What is the primary role of hormone response elements (HREs) in the context of intracellular signaling by hydrophobic hormones?

  • To serve as specific DNA sequences where hormone-receptor complexes bind, influencing gene transcription. (correct)
  • To directly activate cytoplasmic enzymes, initiating a rapid cellular response.
  • To facilitate the diffusion of hydrophobic hormones across the cell membrane.
  • To bind to the hormone, preventing it from interacting with its receptor, thereby regulating hormone activity.
  • How does the mechanism of action for lipid-soluble hormones differ fundamentally from that of hormones utilizing second messengers?

  • Lipid-soluble hormones require transport proteins to enter the cell, while second messengers can diffuse freely across the cell membrane.
  • Lipid-soluble hormones initiate rapid, short-lived responses, while second messengers trigger slower, more sustained effects.
  • Lipid-soluble hormones activate cell surface receptors, while second messengers modulate intracellular signaling pathways.
  • Lipid-soluble hormones directly influence gene transcription, whereas second messengers amplify the initial hormonal signal within the cell. (correct)
  • A mutation in a cell results in the loss of functional hormone receptors in the cytoplasm. Which class of hormones would be least effective in eliciting a response in these mutated cells?

  • Hydrophilic hormones that bind to cell surface receptors.
  • Hydrophobic hormones. (correct)
  • Hormones that utilize a second messenger system.
  • Peptide hormones.
  • Considering the steps involved in Group 1 hormone signaling, what would be the most immediate consequence if a cell lacked the ability to translocate activated receptor complexes to the nucleus?

    <p>The hormone-receptor complex would fail to bind to hormone response elements (HREs) on DNA. (A)</p> Signup and view all the answers

    A researcher is studying a novel hormone that readily diffuses across the cell membrane but does not bind to any known intracellular receptors. What is the most likely mechanism of action for this hormone?

    <p>It alters the permeability of the cell membrane to specific ions. (A)</p> Signup and view all the answers

    Which statement regarding hormone classification based on receptor basis is the MOST accurate?

    <p>Hormone classification by receptor basis considers mechanisms like G-protein-coupled receptors and second messengers. (A)</p> Signup and view all the answers

    A newly discovered hormone is found to have a high affinity for intracellular receptors and significantly impacts gene transcription. Based on its characteristics, which class does this hormone MOST likely belong to?

    <p>Steroid hormone (D)</p> Signup and view all the answers

    Which of the following factors would have the LEAST direct impact on the magnitude of a target cell's response to a hormone?

    <p>The circulating levels of non-specific hormone-binding proteins. (C)</p> Signup and view all the answers

    A researcher is investigating a hormone that triggers a rapid increase in cAMP levels within its target cells. This mechanism of action is MOST characteristic of hormones that bind to which type of receptor?

    <p>G-protein-coupled receptors (B)</p> Signup and view all the answers

    If a person is experiencing a prolonged period of stress, resulting in the constant activation of the fight or flight response, what is LEAST likely to occur?

    <p>Increased intestinal tract activity. (A)</p> Signup and view all the answers

    A pharmaceutical company is developing a drug to mimic the effects of a specific hormone. To maximize the drug's efficacy, they should consider all of the following EXCEPT:

    <p>The patient's blood type. (B)</p> Signup and view all the answers

    Compared to the effects of a peptide hormone, the effects of a steroid hormone are likely to be...

    <p>Slower and more sustained, due to direct effects on gene transcription. (D)</p> Signup and view all the answers

    Which hormone is LEAST likely to be synthesized and secreted at an increased rate in response to sudden, acute stress?

    <p>Thyroxine (B)</p> Signup and view all the answers

    Which characteristic is most critical for a hormone to be classified as lipophilic?

    <p>Capacity to readily diffuse across the cell membrane. (B)</p> Signup and view all the answers

    How does the solubility of a hormone primarily affect its mechanism of action at the target cell?

    <p>Solubility influences whether the hormone binds to a cell-surface or intracellular receptor. (C)</p> Signup and view all the answers

    A researcher is investigating a newly discovered hormone. Initial studies show it is found bound to a protein in the bloodstream. What can be inferred from this observation?

    <p>The hormone is likely hydrophobic and requires a carrier for transport. (A)</p> Signup and view all the answers

    What is the functional consequence of a hydrophilic hormone binding to a cell-surface receptor?

    <p>Initiation of a second messenger cascade to amplify the signal. (C)</p> Signup and view all the answers

    Which of the following mechanisms is exclusively utilized by water-soluble hormones to exert their effects on target cells?

    <p>Activating intracellular signaling cascades via G protein-coupled receptors. (D)</p> Signup and view all the answers

    If a cell is engineered to lack the intracellular receptor for a specific steroid hormone, what outcome is most likely?

    <p>The cell will be unable to respond to the hormone, regardless of hormone concentration. (B)</p> Signup and view all the answers

    A drug is developed that inhibits the production of transport proteins in the bloodstream. What effect would this drug likely have on the activity of lipophilic hormones?

    <p>It would decrease the half-life of lipophilic hormones in the circulation. (B)</p> Signup and view all the answers

    What is a key difference in signal transduction between lipid-soluble and water-soluble hormones?

    <p>Water-soluble hormones typically involve a second messenger system to amplify the signal. (D)</p> Signup and view all the answers

    How does the concentration of hormone in the bloodstream relate to the number of signaling events initiated by the phosphorylation cascade?

    <p>A low hormone concentration can initiate thousands of signaling events due to signal amplification. (D)</p> Signup and view all the answers

    What is the role of phosphodiesterases (PDE) in cAMP signaling pathways?

    <p>To deactivate cAMP, terminating the hormonal signal. (B)</p> Signup and view all the answers

    Which of the following describes the correct sequence of events following the activation of phospholipase C (PLC) by a G-protein?

    <p>PLC cleaves PIP2 into DAG and IP3; DAG activates protein kinases, IP3 triggers calcium release. (B)</p> Signup and view all the answers

    How do calcium ions act as second messengers within the cell after being released by IP3?

    <p>By directly influencing enzymatic activities and binding to calmodulin to modulate protein kinases. (B)</p> Signup and view all the answers

    What is the primary mechanism by which Atrial Natriuretic Peptide (ANP) reduces blood pressure?

    <p>ANP binds to a receptor guanylyl cyclase, increasing cGMP levels and promoting vasodilation. (C)</p> Signup and view all the answers

    How does PKA (Protein Kinase A) affect glycogen metabolism by phosphorylation?

    <p>PKA promotes glycogen breakdown and inhibits glycogen synthesis through phosphorylation of key enzymes. (C)</p> Signup and view all the answers

    What is the key difference between cGMP signaling and cAMP signaling?

    <p>cGMP signaling is GPCR-independent, while cAMP signaling typically involves GPCRs. (C)</p> Signup and view all the answers

    Consider a mutation that permanently activates phosphodiesterase (PDE). What would be the likely effect on a cell's response to hormonal stimulation that elevates cAMP levels?

    <p>The cell would exhibit a reduced and shortened response to the hormonal stimulation. (A)</p> Signup and view all the answers

    A researcher is studying the effects of Atrial Natriuretic Peptide (ANP) on kidney function. Which of the following mechanisms accurately describes how ANP contributes to the reduction of extracellular fluid (ECF) volume?

    <p>ANP promotes increased renal sodium excretion, leading to a reduction in extracellular fluid volume. (B)</p> Signup and view all the answers

    In the context of insulin signaling, what is the MOST direct consequence of autophosphorylation of the insulin receptor following insulin binding?

    <p>Creation of specific binding sites for Insulin Receptor Substrate (IRS-1). (C)</p> Signup and view all the answers

    How does the simultaneous exposure of cells to multiple hormones with diverse mechanisms of action MOST likely affect cellular response?

    <p>The cell integrates the signals from all hormones, resulting in a coordinated and potentially synergistic or antagonistic overall response. (D)</p> Signup and view all the answers

    Which of the following mechanisms BEST explains the pathology of Type 2 Diabetes Mellitus related to defects in hormone receptors?

    <p>Reduced sensitivity or quantity of insulin receptors, resulting in impaired downstream signaling and elevated blood glucose levels. (B)</p> Signup and view all the answers

    In Graves’ disease, autoantibodies target the TSH receptor, leading to hyperthyroidism. Which mechanism BEST describes how these autoantibodies cause thyroid hormone overproduction?

    <p>The autoantibodies bind and activate the TSH receptor, mimicking the effect of TSH and causing increased thyroid hormone production. (C)</p> Signup and view all the answers

    In a sandwich ELISA, what is the PRIMARY purpose of coating the wells of a microtitre plate with a specific antibody?

    <p>To capture the target hormone/antigen present in the patient sample. (D)</p> Signup and view all the answers

    A researcher is developing an ELISA to detect a novel protein associated with a rare autoimmune disorder. To optimize the assay's specificity and minimize cross-reactivity, which strategy would be the MOST effective?

    <p>Using a monoclonal antibody for capture and a different monoclonal antibody, recognizing a distinct epitope of the target protein, for detection. (A)</p> Signup and view all the answers

    A clinical laboratory is evaluating different ELISA methods for detecting HIV antibodies in patient serum. Which consideration is MOST critical in selecting the appropriate ELISA test?

    <p>The ELISA’s documented sensitivity and specificity for detecting HIV antibodies in diverse patient populations. (D)</p> Signup and view all the answers

    In a standard ELISA, at what concentration range of the target analyte does the optical density provide the most sensitive and accurate measurement?

    <p>At concentrations within the linear range of the standard curve, between the upper and lower limits. (D)</p> Signup and view all the answers

    What is the fundamental difference in the interpretation of results between a quantitative and qualitative ELISA?

    <p>Qualitative ELISAs compare the sample to a blank well for a simple 'yes' or 'no' result, while quantitative ELISAs use a standard curve to determine antigen concentration. (A)</p> Signup and view all the answers

    In a competitive ELISA, if a patient sample contains a high concentration of the target antigen, how does this affect the chromogenic signal produced?

    <p>The chromogenic signal is lower because the primary antibody is mostly bound to the patient's antigen, leaving less available to bind to the antigen-coated well. (C)</p> Signup and view all the answers

    In a competitive ELISA, why is the concentration of color inversely proportional to the amount of antigen present in the sample?

    <p>Because a higher concentration of antigen in the sample binds to more of the primary antibody, reducing the amount of free antibody available to bind the antigen on the well, thus reducing the color signal. (B)</p> Signup and view all the answers

    In a competitive ELISA, what does a high optical density (O.D.) reading typically indicate about the concentration of the target antigen in the patient sample?

    <p>A high O.D. indicates a low concentration of the target antigen, as more free antibody is available to bind to the coated wells. (B)</p> Signup and view all the answers

    If a standard ELISA is performed and the optical density readings for patient samples are consistently higher than the upper limit of the standard curve, what is the most appropriate next step?

    <p>Dilute the patient samples and repeat the ELISA to obtain readings within the standard curve range. (C)</p> Signup and view all the answers

    Two patients, A and B, undergo an ELISA test for a specific hormone. Patient A's result falls within the high concentration range, while Patient B's result falls within the low concentration range of the standard curve. Assuming both tests were performed correctly, what can be definitively concluded?

    <p>Patient A has a higher hormone concentration than Patient B. (C)</p> Signup and view all the answers

    Which scenario would necessitate the use of a competitive ELISA over a standard ELISA?

    <p>When the target antigen is small and has limited binding sites, making direct detection difficult. (B)</p> Signup and view all the answers

    Flashcards

    Fight or Flight Response

    A physiological reaction to perceived threat that prepares the body for rapid action.

    Hormone Delivery Factors

    Factors influencing hormones include synthesis rate, proximity to target cells, and conversion rates.

    Receptor Density

    The amount of receptors on a cell influences how it responds to hormones.

    Steroid Hormones

    Hormones derived from cholesterol that are hydrophobic and travel via transport proteins in blood.

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    Peptide Hormones

    Short chains of amino acids, examples include insulin and oxytocin.

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    Amine Hormones

    Hormones derived from modifications of amino acids, like adrenaline and thyroxine.

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    Hydrophilic Hormones

    Water-soluble hormones that are easily transported in the bloodstream.

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    Classification by Solubility

    Hormones can be classified as hydrophilic or lipophilic based on their water solubility.

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    First Messenger

    The initial hormone that carries a signal to a receptor.

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    Second Messenger

    Molecules that relay signals inside cells after receptor activation.

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    Intracellular Signaling

    The process by which hormones convey messages inside the cell.

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    Translocation

    The movement of activated receptors to the nucleus.

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    Hormone Response Elements (HREs)

    Specific DNA segments that activated receptors bind to trigger gene expression.

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    Lipid-soluble hormones

    Hormones that can easily pass through cell membranes to reach intracellular receptors.

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    Water-soluble hormones

    Hormones that cannot diffuse through lipid bilayer and bind to extracellular receptors.

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    Signal receptor

    Proteins that receive signals from hormones to initiate a response.

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    Transport proteins

    Proteins that bind to hydrophobic hormones to transport them in the blood.

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    Hormone classification

    Grouping hormones based on their solubility properties and how they bind.

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    Signaling cascade

    A series of events triggered by hormone-receptor interaction, often using second messengers.

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    Phosphorylation

    The addition of a phosphate group to a protein, often regulating its activity.

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    cAMP

    A second messenger that transmits hormone signals inside cells.

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    G protein-coupled receptors (GPCR)

    Cell surface receptors that respond to external signals and activate intracellular pathways.

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    Phosphodiesterases (PDE)

    Enzymes that deactivate cAMP and other second messengers, turning off signals.

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    IP3

    A second messenger that helps release calcium ions from storage within the cell.

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    Calmodulin

    A calcium-binding protein that modulates the activity of various proteins upon binding to calcium.

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    Guanylyl cyclase

    An enzyme that converts GTP to cGMP, functioning independently of GPCR.

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    Atrial natriuretic peptide (ANP)

    A hormone released when blood pressure rises, activating guanylyl cyclase to increase cGMP.

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    ELISA

    A test that measures antigen concentrations using antibodies.

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    Standard Curve

    A graph used in ELISA to determine unknown antigen concentrations by comparing them to known standards.

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    Competitive ELISA

    A type of ELISA where the sample competes with antigen-coated wells for antibody binding.

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    Optical Density (O.D.)

    A measure of absorbance in an ELISA, indicating the signal strength based on antigen concentration.

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    Quantitative ELISA

    ELISA providing numerical data about antigen concentration via a standard curve.

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    Qualitative ELISA

    ELISA giving a yes/no answer about antigen presence rather than precise amounts.

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    Chromogenic Signal

    Color change produced in an ELISA due to enzyme-substrate reaction, indicating antigen levels.

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    Limit of Detection

    The lowest concentration of antigen that can be reliably detected in an assay.

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    Insulin Receptor

    A tetramer receptor that is a receptor tyrosine kinase involved in glucose regulation.

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    Autophosphorylation

    When ligand binding causes receptors to phosphorylate themselves at tyrosine residues.

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    Type 2 Diabetes

    A condition characterized by reduced sensitivity of insulin receptors leading to high blood glucose.

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    Graves' Disease

    An autoimmune disease where antibodies bind to TSH receptor, causing excessive thyroid hormone production.

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    Sandwich ELISA

    A type of ELISA where an antigen is captured between two antibodies for detection.

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    Study Notes

    Course Information

    • Course: Endocrine and Breast
    • Title: Cellular Mechanisms of Hormone Action
    • Lecturer: Prof Will Ford
    • Date: January 2025
    • Location: Rm 337

    Learning Objectives

    • Describe the role and mechanism of action of hormones in the human body.
    • Differentiate between lipophilic (e.g., estrogen) and hydrophilic (e.g., adrenaline) hormones.
    • Distinguish between how Group 1 and Group 2 hormones drive changes in cell state.
    • Describe how steroid hormones use hormone response elements (HREs) to regulate gene transcription.
    • Discuss how hydrophilic hormone signaling amplifies the hormone signal through second messenger cascades.
    • Explain how defects in hormone responses can cause disease.
    • Explain how hormonal receptor defects can cause disease.
    • Explain how ELISA works for measuring hormone levels.

    Two Systems Coordinating Communication

    • The endocrine system secretes hormones for slower, long-acting responses (reproduction, development, energy, metabolism, growth, behavior).
    • The nervous system uses high-speed electrical signals (along neurons) for rapid communication, regulating other cells.

    Endocrine System

    • Hormones are biochemical messengers secreted by endocrine glands, impacting gene expression and protein state.
    • Hormones work in tandem with neurotransmitters (adjacent cell contact).
    • Endocrine glands involved: Pineal, Hypothalamus, Pituitary, Thyroid/Parathyroid, Thymus, Ovary, Testicle, Pancreas, Adrenal, Placenta.

    Regulation within Endocrine System

    • Most hormones are regulated by feedback mechanisms, in which the product feeds back to control its production.
    • Most feedback mechanisms are negative feedback loops, keeping hormone concentrations in a narrow range.
    • Positive feedback reinforces the initial stimulus, increasing the response/hormone production.

    Hormonal Signaling

    • Endocrine signaling typically describes hormones acting on distant sites.
    • Hormones can also act locally:
      • Paracrine signaling: target cells near the secreting cells.
      • Autocrine signaling: the target cell is also the secreting cell.

    Hormone Selectivity and Potency

    • Hormones are highly selective and potent (10⁻⁹ - 10⁻¹⁵ M) compared to other molecules (10⁻⁵ - 10⁻³ M).
    • This selectivity and potency result from receptors specific to certain hormones.
    • Cells express receptors for specific hormones.

    Hormones: Basic Principles

    • A stimulus triggers an endocrine gland to release hormones into the blood.
    • Hormones act on target tissues with high specificity at receptors.
    • Hormone actions include changing plasma membrane permeability, regulating protein expressions, changing enzyme activity, influencing secretion and stimulating cell division.
    • Hormone action is monitored and controlled via feedback mechanisms, primarily negative feedback.

    Endocrine System Functions

    • Includes glands: Hypothalamus, Pituitary, Thyroid, Parathyroid, Islets cells, Testes, Ovaries, Adrenal cortex, Adrenal medulla, Pineal gland.
    • Specific hormones, examples: Growth hormone, Vasopressin, Thyroxine, Calcitonin, Parathyroid hormone, Insulin, Glucagon, Testosterone, Estrogen, Adrenaline, Glucocorticoids, Aldosterone, Melatonin.

    Hormone Classification

    • Classified by Chemical nature: steroids, peptides, glycoproteins.
    • Classified by Solubility: lipophilic (hydrophobic) vs. hydrophilic (water-soluble).
    • Classified by Binding Site: intracellular vs. cell surface.
    • Classified by Receptor basis: G-protein-coupled receptors, Second messengers, Kinase receptors.

    Diversity in Hormone Structure

    • Steroid Hormones: derived from cholesterol, not water-soluble (travel bound to a transport protein).
    • Peptide/Proteins Hormones: chains of amino acids, varying lengths.
    • Amine Hormones: derived from amino acids.

    Hormone Classification based on Solubility

    • Water-soluble hormones are readily transported in the blood.
    • Lipid-soluble hormones bind to transport proteins for circulation.

    Classification of hormones based on solubility (Group I & II)

    • Group I: Hydrophobic: Steroids, Iodotyronines. Plasma transport bound. Long half-life. Intracellular receptor. Slow, developmental effects.
    • Group II: Hydrophilic: Peptides, Proteins, Catecholamines. Plasma transport free. Short half-life. Cell membrane receptor. Rapid, metabolic effects.

    Steps in Group 1 (Hydrophobic) Intracellular Signaling

    • Diffusion: Hydrophobic hormones pass through the lipid bilayer.
    • Binding: Hormones bind to specific intracellular receptors within the cell.
    • Translocation: Receptor-hormone complex translocates to the nucleus.
    • Hormone Response Element (HRE) Binding: Receptor-hormone complex binds to HREs in DNA.
    • Gene expression: Binding alters mRNA and protein production.

    Steps in Group 2 (Hydrophilic) Signaling

    • Binding: Hormone binds to a specific membrane receptor.
    • Intracellular Signaling: Initiates a cascade involving second messengers (e.g., cAMP, IP3/Ca²⁺).
    • Activation: Second messengers activate intracellular enzymes.
    • Phosphorylation: Enzymes phosphorylate proteins, altering cellular activity.

    Other Second Messengers

    • Other second messengers exist, including cAMP, IP3/Ca²⁺, and cGMP.
    • These systems participate in signaling cascades, mediating various cellular responses.

    Negative Feedback control of cAMP Signaling

    • Phosphodiesterases (PDEs) break down cAMP, turning off the signaling cascade.

    Hormone Receptors

    • Insulin receptor - receptor tyrosine kinase.
    • Autophosphorylation: Ligand binding initiates phosphorylation of tyrosine resides on the receptor.
    • Propagation of signal: Phosphorylated sites on the receptor activate downstream components, leading to responses such as increasing glucose uptake and glycogen production.

    Hormone Receptor Defects

    • Defects in hormone receptors can cause various diseases, examples include Type 2 diabetes, and Graves' disease.
    • Type 2: Insulin resistance due to reduced/insensitive insulin receptors, leading to increased blood sugar levels.
    • Graves': Autoantibodies binding to the TSH receptor, causing increased thyroid hormone production and hyperthyroidism.

    ELISA (Enzyme-linked immunosorbent assay)

    • ELISA is a technique to quantify or detect hormone levels.
    • Two Main Types: Sandwich and Competitive.
    • Sandwich: Antibody-coated wells, capture antigen, second antibody linked to enzyme, substrate used to detect antigen.
    • Competitive: Antibody-coated wells, capture antigen, sample antibody, substrate used to detect amount of antigen.

    Hormonal Action: Coordination

    • Cells respond to multiple hormones simultaneously.
    • Hormone mechanisms coordinate to produce complex effects.

    Standards and Limits of Detection

    • Standard curves define the relationship between optical density (color intensity) and hormone concentration.
    • Upper and Lower Limits (of detection) are critical components for accuracy in ELISA tests using standard curves.

    Summary of study notes

    • This document details the fundamental principles behind hormonal action, from the basics of different types of hormones, to signaling cascades, regulation, and measurement/detection using ELISA. It covers both hydrophobic (intracellular) and hydrophilic hormone-receptor signaling pathways, and explains how their defects can trigger diseases.

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    Description

    Explore intracellular signaling by hydrophobic hormones, focusing on hormone response elements (HREs) and receptor function. Compare the mechanisms of lipid-soluble hormones with those using second messengers. Investigate the consequences of receptor mutations and impaired nuclear translocation.

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