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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?
What is the primary role of hormone response elements (HREs) in the context of intracellular signaling by hydrophobic hormones?
How does the mechanism of action for lipid-soluble hormones differ fundamentally from that of hormones utilizing second messengers?
How does the mechanism of action for lipid-soluble hormones differ fundamentally from that of hormones utilizing second messengers?
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?
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?
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?
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?
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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?
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?
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Which statement regarding hormone classification based on receptor basis is the MOST accurate?
Which statement regarding hormone classification based on receptor basis is the MOST accurate?
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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?
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?
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Which of the following factors would have the LEAST direct impact on the magnitude of a target cell's response to a hormone?
Which of the following factors would have the LEAST direct impact on the magnitude of a target cell's response to a hormone?
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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?
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?
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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?
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?
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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:
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:
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Compared to the effects of a peptide hormone, the effects of a steroid hormone are likely to be...
Compared to the effects of a peptide hormone, the effects of a steroid hormone are likely to be...
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Which hormone is LEAST likely to be synthesized and secreted at an increased rate in response to sudden, acute stress?
Which hormone is LEAST likely to be synthesized and secreted at an increased rate in response to sudden, acute stress?
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Which characteristic is most critical for a hormone to be classified as lipophilic?
Which characteristic is most critical for a hormone to be classified as lipophilic?
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How does the solubility of a hormone primarily affect its mechanism of action at the target cell?
How does the solubility of a hormone primarily affect its mechanism of action at the target cell?
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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?
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?
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What is the functional consequence of a hydrophilic hormone binding to a cell-surface receptor?
What is the functional consequence of a hydrophilic hormone binding to a cell-surface receptor?
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Which of the following mechanisms is exclusively utilized by water-soluble hormones to exert their effects on target cells?
Which of the following mechanisms is exclusively utilized by water-soluble hormones to exert their effects on target cells?
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If a cell is engineered to lack the intracellular receptor for a specific steroid hormone, what outcome is most likely?
If a cell is engineered to lack the intracellular receptor for a specific steroid hormone, what outcome is most likely?
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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?
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?
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What is a key difference in signal transduction between lipid-soluble and water-soluble hormones?
What is a key difference in signal transduction between lipid-soluble and water-soluble hormones?
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How does the concentration of hormone in the bloodstream relate to the number of signaling events initiated by the phosphorylation cascade?
How does the concentration of hormone in the bloodstream relate to the number of signaling events initiated by the phosphorylation cascade?
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What is the role of phosphodiesterases (PDE) in cAMP signaling pathways?
What is the role of phosphodiesterases (PDE) in cAMP signaling pathways?
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Which of the following describes the correct sequence of events following the activation of phospholipase C (PLC) by a G-protein?
Which of the following describes the correct sequence of events following the activation of phospholipase C (PLC) by a G-protein?
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How do calcium ions act as second messengers within the cell after being released by IP3?
How do calcium ions act as second messengers within the cell after being released by IP3?
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What is the primary mechanism by which Atrial Natriuretic Peptide (ANP) reduces blood pressure?
What is the primary mechanism by which Atrial Natriuretic Peptide (ANP) reduces blood pressure?
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How does PKA (Protein Kinase A) affect glycogen metabolism by phosphorylation?
How does PKA (Protein Kinase A) affect glycogen metabolism by phosphorylation?
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What is the key difference between cGMP signaling and cAMP signaling?
What is the key difference between cGMP signaling and cAMP signaling?
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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?
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?
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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?
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?
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In the context of insulin signaling, what is the MOST direct consequence of autophosphorylation of the insulin receptor following insulin binding?
In the context of insulin signaling, what is the MOST direct consequence of autophosphorylation of the insulin receptor following insulin binding?
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How does the simultaneous exposure of cells to multiple hormones with diverse mechanisms of action MOST likely affect cellular response?
How does the simultaneous exposure of cells to multiple hormones with diverse mechanisms of action MOST likely affect cellular response?
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Which of the following mechanisms BEST explains the pathology of Type 2 Diabetes Mellitus related to defects in hormone receptors?
Which of the following mechanisms BEST explains the pathology of Type 2 Diabetes Mellitus related to defects in hormone receptors?
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In Graves’ disease, autoantibodies target the TSH receptor, leading to hyperthyroidism. Which mechanism BEST describes how these autoantibodies cause thyroid hormone overproduction?
In Graves’ disease, autoantibodies target the TSH receptor, leading to hyperthyroidism. Which mechanism BEST describes how these autoantibodies cause thyroid hormone overproduction?
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In a sandwich ELISA, what is the PRIMARY purpose of coating the wells of a microtitre plate with a specific antibody?
In a sandwich ELISA, what is the PRIMARY purpose of coating the wells of a microtitre plate with a specific antibody?
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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?
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?
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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?
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?
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In a standard ELISA, at what concentration range of the target analyte does the optical density provide the most sensitive and accurate measurement?
In a standard ELISA, at what concentration range of the target analyte does the optical density provide the most sensitive and accurate measurement?
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What is the fundamental difference in the interpretation of results between a quantitative and qualitative ELISA?
What is the fundamental difference in the interpretation of results between a quantitative and qualitative ELISA?
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In a competitive ELISA, if a patient sample contains a high concentration of the target antigen, how does this affect the chromogenic signal produced?
In a competitive ELISA, if a patient sample contains a high concentration of the target antigen, how does this affect the chromogenic signal produced?
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In a competitive ELISA, why is the concentration of color inversely proportional to the amount of antigen present in the sample?
In a competitive ELISA, why is the concentration of color inversely proportional to the amount of antigen present in the sample?
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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?
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?
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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?
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?
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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?
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?
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Which scenario would necessitate the use of a competitive ELISA over a standard ELISA?
Which scenario would necessitate the use of a competitive ELISA over a standard ELISA?
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Flashcards
Fight or Flight Response
Fight or Flight Response
A physiological reaction to perceived threat that prepares the body for rapid action.
Hormone Delivery Factors
Hormone Delivery Factors
Factors influencing hormones include synthesis rate, proximity to target cells, and conversion rates.
Receptor Density
Receptor Density
The amount of receptors on a cell influences how it responds to hormones.
Steroid Hormones
Steroid Hormones
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Peptide Hormones
Peptide Hormones
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Amine Hormones
Amine Hormones
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Hydrophilic Hormones
Hydrophilic Hormones
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Classification by Solubility
Classification by Solubility
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First Messenger
First Messenger
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Second Messenger
Second Messenger
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Intracellular Signaling
Intracellular Signaling
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Translocation
Translocation
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Hormone Response Elements (HREs)
Hormone Response Elements (HREs)
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Lipid-soluble hormones
Lipid-soluble hormones
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Water-soluble hormones
Water-soluble hormones
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Signal receptor
Signal receptor
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Transport proteins
Transport proteins
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Hormone classification
Hormone classification
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Signaling cascade
Signaling cascade
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Phosphorylation
Phosphorylation
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cAMP
cAMP
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G protein-coupled receptors (GPCR)
G protein-coupled receptors (GPCR)
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Phosphodiesterases (PDE)
Phosphodiesterases (PDE)
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IP3
IP3
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Calmodulin
Calmodulin
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Guanylyl cyclase
Guanylyl cyclase
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Atrial natriuretic peptide (ANP)
Atrial natriuretic peptide (ANP)
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ELISA
ELISA
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Standard Curve
Standard Curve
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Competitive ELISA
Competitive ELISA
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Optical Density (O.D.)
Optical Density (O.D.)
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Quantitative ELISA
Quantitative ELISA
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Qualitative ELISA
Qualitative ELISA
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Chromogenic Signal
Chromogenic Signal
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Limit of Detection
Limit of Detection
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Insulin Receptor
Insulin Receptor
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Autophosphorylation
Autophosphorylation
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Type 2 Diabetes
Type 2 Diabetes
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Graves' Disease
Graves' Disease
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Sandwich ELISA
Sandwich ELISA
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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.