Hydrophobic Hormones and Intracellular Signaling
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Questions and Answers

What is the first step in the intracellular signaling process for hydrophobic hormones?

  • Hormone Response Elements interaction
  • Diffusion (correct)
  • Binding
  • Translocation

Which of the following actions occurs after a hydrophobic hormone binds to its specific receptor?

  • The receptor is translocated to the nucleus. (correct)
  • Gene transcription is immediately initiated.
  • The hormone dissociates from the receptor.
  • An enzyme is activated to produce a second messenger.

What role do hormone response elements (HREs) play in the action of hydrophobic hormones?

  • They help in the diffusion of hormones through the membrane.
  • They bind to activated receptors to start gene transcription. (correct)
  • They trigger the rapid generation of ATP.
  • They activate secondary messengers.

In the context of intracellular signaling, which type of hormones are known to diffuse easily across the cell membrane?

<p>Hydrophobic hormones (C)</p> Signup and view all the answers

What is the final outcome of the intracellular signaling process initiated by hydrophobic hormones?

<p>Transcription of target genes into mRNA (D)</p> Signup and view all the answers

What defines the primary mechanism by which steroid hormones regulate gene transcription?

<p>Binding to hormone response elements (HREs) (C)</p> Signup and view all the answers

How do hydrophilic hormones primarily amplify their signal in target cells?

<p>By potentiating a second messenger cascade (B)</p> Signup and view all the answers

What complication can arise from defects in hormone signaling pathways?

<p>Development of hormonal imbalances and diseases (A)</p> Signup and view all the answers

In an ELISA test, what is typically indicated by a high concentration of antigen?

<p>High signal with low complexed antibody (D)</p> Signup and view all the answers

Which of the following correctly describes the characteristics of lipophilic hormones?

<p>They can passively diffuse through cell membranes and interact with intracellular receptors (C)</p> Signup and view all the answers

Which mechanism is primarily activated by cGMP in the context of hormone action?

<p>Activation of protein kinase G (A)</p> Signup and view all the answers

What is the primary role of the insulin receptor's autophosphorylation process?

<p>To activate downstream signaling via IRS-1 (B)</p> Signup and view all the answers

Which condition is directly linked to defects in insulin receptors?

<p>Type 2 diabetes (B)</p> Signup and view all the answers

What is the function of the ELISA technique?

<p>To quantify targeted antibodies (A)</p> Signup and view all the answers

In a Sandwich ELISA, which component binds to the well first?

<p>The primary antibody specific for the antigen (D)</p> Signup and view all the answers

What is the effect of autoantibodies binding to the TSH receptor in Graves' disease?

<p>Stimulated thyroid hormone production leading to hyperthyroidism (C)</p> Signup and view all the answers

What condition results from the reduction or insensitivity of the insulin receptor?

<p>Increased blood glucose levels (A)</p> Signup and view all the answers

Why are antibodies used in ELISA techniques?

<p>To specifically label target hormones (D)</p> Signup and view all the answers

What role do hormone response elements (HREs) play in gene regulation?

<p>They associate with activated receptors and further transcription factors to regulate gene expression. (D)</p> Signup and view all the answers

Which statement correctly describes the mechanism of steroid hormone action?

<p>They can penetrate cell membranes and bind to intracellular receptors to modify gene expression. (A)</p> Signup and view all the answers

Why do steroid hormones often require carrier molecules?

<p>To enhance their stability and solubility in the bloodstream. (C)</p> Signup and view all the answers

In the context of hormone signaling, what is the first step for hydrophilic hormones?

<p>They bind to specific receptors on the cell membrane. (A)</p> Signup and view all the answers

What is the function of protein kinase A (PKA) in cellular signaling?

<p>To activate signaling pathways by phosphorylating target proteins. (C)</p> Signup and view all the answers

What type of receptors do steroid hormones primarily bind to after crossing the plasma membrane?

<p>Intracellular receptors located in the cytoplasm or nucleus (B)</p> Signup and view all the answers

Which sequence describes the role of G-proteins in hormone signaling?

<p>They activate adenylyl cyclase, leading to the formation of cAMP. (B)</p> Signup and view all the answers

How do hormone-receptor complexes influence mRNA and protein expression?

<p>They enhance the transcription of specific genes by interacting with DNA. (C)</p> Signup and view all the answers

What does a standard curve in ELISA primarily help determine?

<p>Quantitative concentration of antigens in patient samples (D)</p> Signup and view all the answers

In a competitive ELISA, what happens when there is a high concentration of antigen in the patient sample?

<p>Less chromogenic signal is produced (A)</p> Signup and view all the answers

What is the relationship between optical density and antigen concentration in a typical ELISA?

<p>Optical density is directly proportional to antigen concentration (D)</p> Signup and view all the answers

Which type of result would a qualitative ELISA commonly provide?

<p>Presence or absence of an antigen (B)</p> Signup and view all the answers

Why is it important to have a serial dilution of known antigen in an ELISA?

<p>To create a standard curve for quantification (C)</p> Signup and view all the answers

What is indicated by the lower limit of the detection range in an ELISA?

<p>Little to no increase in signal with increased concentration (D)</p> Signup and view all the answers

In a competitive ELISA, what does a decrease in the amount of free antibody indicate?

<p>Increased concentration of antigen in the sample (B)</p> Signup and view all the answers

What does the optical density reflect in relation to the amount of target concentration in ELISA?

<p>It is a sensitive measure of the target concentration (D)</p> Signup and view all the answers

What role do hormone response elements (HREs) play in the action of steroid hormones?

<p>They regulate the transcription of genes signalled by the steroid hormone. (A)</p> Signup and view all the answers

Which of the following correctly describes the difference between Group 1 and Group 2 hormones?

<p>Group 1 hormones bind to surface receptors, Group 2 bind intracellularly. (A)</p> Signup and view all the answers

How do hydrophilic hormones amplify their signals in target cells?

<p>By potentiating a second messenger cascade. (C)</p> Signup and view all the answers

What is the primary mechanism by which most hormones are regulated?

<p>Negative feedback mechanisms that maintain hormone concentrations. (A)</p> Signup and view all the answers

In endocrine signaling, what term describes the action where hormones affect distant target cells?

<p>Endocrine signaling. (D)</p> Signup and view all the answers

What characteristic of hormones allows them to elicit potent biological responses at very low concentrations?

<p>The specificity of their receptors and their low concentrations. (B)</p> Signup and view all the answers

What type of hormones are testosterone and oestrogen classified as?

<p>Lipophilic hormones. (D)</p> Signup and view all the answers

Which hormone is primarily responsible for increasing blood sugar by stimulating glycogen breakdown in the liver?

<p>Glucagon. (D)</p> Signup and view all the answers

What impact do defects in hormonal receptors have on the body?

<p>They can lead to diseases by disrupting normal hormone signaling. (B)</p> Signup and view all the answers

Which hormone acts as the master regulator of the endocrine system?

<p>Hypothalamic hormones. (C)</p> Signup and view all the answers

What is the typical concentration range for hormones in the bloodstream?

<p>10-9 – 10-15 M. (C)</p> Signup and view all the answers

What is the primary function of aldosterone in the body?

<p>Regulates sodium content in the blood. (C)</p> Signup and view all the answers

How does adrenaline primarily affect the body during stress?

<p>By stimulating the 'fight or flight' response. (B)</p> Signup and view all the answers

Flashcards

First Messenger

A molecule that binds to a specific receptor on a cell, initiating a signaling cascade.

Second Messenger

A molecule that relays a signal from a first messenger to intracellular targets.

Signal Receptor

A protein that binds to a specific hormone or ligand, initiating a signal transduction pathway.

Cytoplasmic Response

A process by which a cell responds to a signal from a hormone or other ligand.

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Gene Regulation

The process by which a hormone or other ligand alters gene expression.

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Hormones

Chemical messengers released by endocrine glands that influence gene expression and protein activity, coordinating various bodily functions.

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Endocrine system

A communication system that uses hormones to regulate slower, long-lasting processes like growth, reproduction, and metabolism.

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Nervous system

A communication system using electrical impulses to transmit rapid responses in the body.

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Endocrine signaling

A type of cell signaling where the hormone acts on a distant target.

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Paracrine signaling

A type of cell signaling where the hormone acts on neighboring cells.

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Autocrine signaling

A type of cell signaling where the hormone acts on the same cell that released it.

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Hormone potency

The concentration of hormones required to elicit a response is extremely low, ranging from 10^-9 to 10^-15 M.

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Hormone selectivity

Cells have specific receptors that bind to particular hormones, ensuring only target cells respond.

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Hormone feedback mechanisms

Mechanisms that regulate the production of hormones, often involving the product feeding back to control its own synthesis.

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Negative feedback

A type of feedback mechanism where the product of a process inhibits its own further production, maintaining a stable level.

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Positive feedback

A type of feedback mechanism where the product of a process amplifies its own production, leading to a snowball effect.

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Lipophilic hormones (Group 1)

Hormones like estrogen and testosterone that are lipid-soluble and can pass through cell membranes.

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Hydrophilic hormones (Group 2)

Hormones like adrenaline or insulin that are water-soluble and can't easily cross cell membranes.

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Hormone response elements (HREs)

A protein complex inside cells that binds to steroid hormones, triggering gene transcription.

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Second messenger cascade

A series of molecular events triggered by hydrophilic hormones, amplifying the signal and leading to a cellular response.

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G-protein-coupled Receptor (GPCR)

A type of receptor that sits on the cell membrane and binds to hydrophilic hormones, initiating a signal transduction pathway.

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G-protein

A protein that relays a signal from an activated receptor to another protein, typically an enzyme, in a signal transduction pathway.

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Adenylyl Cyclase

An enzyme that converts ATP into cAMP, a second messenger that amplifies the signal within the cell.

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Cyclic AMP (cAMP)

A second messenger molecule that relays the signal from an activated G-protein to other intracellular targets, such as protein kinase A.

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Protein Kinase A (PKA)

An enzyme that is activated by cAMP, which phosphorylates other proteins, leading to changes in gene expression and cell function.

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Intracellular Receptor

A protein that binds to a specific hormone, typically a steroid hormone, and then translocates to the nucleus to regulate gene expression.

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Nuclear Receptor

A type of intracellular receptor that binds to steroid hormones and then interacts with specific DNA sequences to regulate gene expression.

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Atrial Natriuretic Peptide (ANP)

A peptide hormone that acts on the kidneys to reduce extracellular fluid (ECF) volume by increasing sodium excretion.

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Signal Transduction

The process by which a hormone binds to its receptor and initiates a chain of events that ultimately leads to a specific cellular response.

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Receptor Tyrosine Kinase (RTK)

A type of receptor that has intrinsic enzymatic activity, specifically protein kinase activity. When a hormone binds, it activates the kinase domain, leading to phosphorylation of downstream targets.

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Autophosphorylation

The phosphorylation of tyrosine residues on a protein, often triggered by a hormone-receptor interaction.

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Insulin Receptor Substrate (IRS-1)

A protein that acts as an intermediary in insulin signaling pathways. It binds to the phosphorylated insulin receptor and gets phosphorylated itself, amplifying the signal.

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ELISA (Enzyme-Linked Immunosorbent Assay)

A common laboratory technique used to detect and quantify the presence of specific antigens or antibodies in a sample.

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Sandwich ELISA

A type of ELISA that uses two antibodies to capture and detect the target molecule. It offers high sensitivity and specificity.

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ELISA

An enzyme-linked immunosorbent assay (ELISA) is a common laboratory technique used to detect and quantify specific antigens in biological samples, such as blood, serum, or urine. It relies on the specific binding of an antibody to its target antigen.

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Standard Curve in ELISA

A standard curve is a graph that relates the signal intensity of different concentrations of a known standard antigen to the corresponding concentrations. This graph is used to determine the unknown antigen concentration in the patient sample by comparing its signal to the standard curve

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Limit of Detection (LoD)

The limit of detection (LoD) is the lowest concentration of an analyte which can be reliably detected by an analytical method. In ELISA, it signifies the lowest detectable concentration based on the assay's sensitivity.

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ELISA Principle

The principle behind ELISA is the specific interaction between antibodies (Ab) and antigens. The antibody is linked to an enzyme that generates a signal when it encounters its substrate. This signal is directly proportional to the amount of antigen present in the sample.

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Competitive ELISA

A competitive ELISA utilizes a fixed amount of antibody, and the signal strength is inversely proportional to the concentration of target antigen in the sample. This is because more antigen in the sample means less antibody is free to bind to the well, leading to a lower signal.

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Qualitative ELISA

Qualitative ELISA is used to determine the presence or absence of an antigen but does not measure its concentration. It provides a yes/no answer, like a pregnancy test or HIV test.

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Quantitative ELISA

Quantitative ELISA measures the concentration of a specific antigen in a sample. Its results are expressed as units of concentration, often using a standard curve to determine the values.

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Optical Density (O.D.)

The optical density (O.D.) is a measure of how much light is absorbed by a solution. In ELISA, a higher O.D. value typically indicates a higher concentration of the analyte in the sample.

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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 hormones in the human body
  • Differentiate between lipophilic (e.g., estrogen) and hydrophilic (e.g., adrenaline) hormones
  • Distinguish how hormones (Group 1 & 2) create changes in cell state
  • Describe how steroid hormones use hormone response elements (HREs) to regulate gene transcription
  • Discuss how hydrophilic hormones use 2nd messenger cascades to amplify their signal
  • Explain how defects in hormone responses can cause disease
  • Explain how hormonal receptor defects can cause disease
  • Explain how ELISA works in measuring hormone levels

Two Systems Coordinating Communication

  • The endocrine system releases hormones for slower, long-acting responses (e.g., reproduction, development, metabolism, growth, behavior)
  • The nervous system transmits high-speed electrical signals along neurons to regulate other cells

The Endocrine System

  • Hormones are biochemical messengers
  • Released by endocrine glands
  • Impact gene expression and protein state
  • Complement neurotransmitters

Regulation Within the Endocrine System

  • Most hormones are regulated via feedback mechanisms
  • Positive feedback loops amplify the initial stimulus
  • Negative feedback loops maintain hormone concentration within a narrow range

Hormonal Signalling

  • Endocrine signaling acts on distant cells
  • Paracrine signaling acts on nearby cells
  • Autocrine signaling acts on the secreting cell itself

Hormones: Highly Selective and Potent

  • Hormones have very high selectivity and potency
  • This is due to specific receptors on target cells

Hormones: Basic Principles

  • A stimulus triggers the endocrine gland to produce hormones and release them into the blood
  • These hormones carry signals to target tissues
  • Hormone actions include: altering plasma membrane permeability, regulating functional protein expression, modulating enzyme activity, and influencing secretory product release and mitosis.
  • Hormonal changes are monitored and controlled by a feedback mechanism, most often negative feedback.

Endocrine System: General Functions

  • A table that details various glands and their associated hormones, along with their general functions and impact on different bodily systems (e.g., growth, skeletal system, metabolism, circulatory system, digestive system, immunity, reproduction).

Multiple Choice Question 1 - Adrenaline

  • Correct answer: It plays an important role in the fight-or-flight response

Factors Influencing Cellular Response

  • Hormone delivery (synthesis, secretion rate, proximity to target cell, transport protein dissociation, rate of conversion/clearance by liver/kidney)
  • Receptor status (density, occupancy, affinity, desensitization)

Hormone Classification

  • Classification by chemical nature (steroids, peptides, glycoproteins)
  • Solubility (hydrophilic vs. hydrophobic)
  • Cellular binding site (intracellular vs. cell surface)
  • Receptor basis (G-protein coupled receptors, second messengers, kinase receptors)

Diversity in Hormone Structure (chemical makeup)

  • Steroid hormones (derived from cholesterol)
  • Peptide hormones (short chains of amino acids)
  • Protein/glycoprotein hormones (longer chains)
  • Amine hormones (amino acid derivatives)

Hormone Classification Based on Solubility

  • Water-soluble (hydrophilic) hormones travel freely in the blood
  • Lipid-soluble (hydrophobic) hormones require carrier proteins for transport

Classification of Hormones Based on Solubility (Group 1 & 2)

  • A table that contrasts Group I (hydrophobic) and Group II (hydrophilic) hormones based on solubility, chemical nature, plasma transport, half-life, target cell receptor location, and general effects.

Classification of Hormones Based on Cellular Binding Site

  • Hydrophilic hormones cannot cross the cell membrane and bind to receptors on the cell surface
  • Lipophilic hormones can cross the cell membrane and bind to intracellular receptors

Steps in Group 1 Hormone (hydrophobic) Intracellular Signaling

  • Diffusion through the membrane
  • Binding to intracellular receptors
  • Translocation to the nucleus
  • Binding to hormone response elements (HREs) on DNA
  • Driving changes to mRNA and protein expression

Steps in Group 2 Hormone (hydrophilic) Signaling

  • Binding to cell membrane receptors
  • Activation of intracellular signaling pathways (e.g., G protein, second messengers)
  • Activation of protein kinases
  • Phosphorylation of cellular proteins (e.g., metabolic enzymes, transcription factors)

Other Second Messengers

  • Several secondary messenger systems exist (cAMP, IP₃/calcium, cGMP)
  • Each one works in a specific cascade to amplify the initial hormone signal

Phosphodiesterases (PDE) and Negative Feedback

  • Phosphodiesterase (PDE) enzymes break down second messengers (e.g., cAMP)
  • This deactivation turns off the signal and provides negative feedback to control the duration of the hormone response

ELISA - Enzyme-Linked Immunosorbent Assay

  • General principles of ELISA—using antibodies for target labeling, high specificity, and quantification
  • Different ELISA types (direct, indirect, sandwich, competitive)
  • Examples in various applications (tuberculosis, hepatitis B, HIV, pregnancy, thyroid hormone)
  • Standard curve and limits of detection
  • Details about sandwich and competitive ELISA principles

Hormone Receptor Defects and Disease

  • Defects in hormone receptors can cause various diseases (e.g., type 2 diabetes, Graves' disease)

Hormones Drive a Variety of Biological Processes

  • Hormones trigger a coordinated response with other molecules and systems to maintain homeostasis.

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Description

This quiz explores the processes involved in intracellular signaling for hydrophobic hormones. Test your knowledge on the steps that follow hormone binding, the role of hormone response elements, and the characteristics of these hormones. Understanding these concepts is essential for grasping endocrine signaling mechanisms.

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