GPCR Signaling and Downstream Effects
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Questions and Answers

A researcher is investigating a novel GPCR signaling pathway and observes that activation leads to a rapid increase in cytosolic calcium levels. Knowing this, which of the following interventions would MOST directly inhibit this immediate calcium release?

  • Application of a membrane-impermeable chelator to bind extracellular calcium.
  • Overexpression of phosphodiesterase (PDE) to rapidly degrade cAMP.
  • Administration of a non-hydrolyzable analog of GTP to prevent G-protein activation.
  • Introduction of a cell-permeable, competitive inhibitor of phospholipase C (PLC). (correct)

In a cell line with constitutively active PKA, which genetic manipulation would MOST effectively reduce glycogen breakdown?

  • Introduction of a constitutively active mutant of protein phosphatase 1 (PP1). (correct)
  • Knockout of the gene encoding glycogen phosphorylase kinase (PhK).
  • Inhibition of adenylyl cyclase activity via a G protein coupled receptor agonist.
  • Overexpression of a dominant-negative mutant of phosphodiesterase (PDE).

A pharmaceutical company is developing a drug to selectively enhance cGMP signaling in vascular smooth muscle cells to treat hypertension. Which of the following mechanisms of action would be MOST appropriate for this drug?

  • Activation of adenylyl cyclase.
  • Direct antagonism of the atrial natriuretic peptide (ANP) receptor.
  • Inhibition of phosphodiesterase 5 (PDE5). (correct)
  • Upregulation of IP3 receptor expression.

A researcher discovers a novel mutation in a G protein-coupled receptor (GPCR) that results in its constitutive activation, even in the absence of its ligand. If this mutation specifically affects the receptor's interaction with Gαs, which of the following downstream effects would be MOST likely observed?

<p>Elevated levels of cAMP and subsequent activation of protein kinase A (PKA). (A)</p> Signup and view all the answers

An investigator is studying the effects of a specific hormone on liver cells and observes a significant increase in glycogen breakdown. They hypothesize that this effect is mediated by cAMP. Which of the following experimental results would STRONGLY support this hypothesis?

<p>Pre-treating the cells with a phosphodiesterase inhibitor significantly enhances the hormone's effect on glycogen breakdown. (C)</p> Signup and view all the answers

Researchers are investigating a cellular response to a novel ligand. They observe that ligand binding to its receptor leads to activation of phospholipase C (PLC) and subsequent generation of IP3. Which of the following scenarios would LEAST likely occur as a direct consequence of IP3 production?

<p>Decreased intracellular calcium concentration. (D)</p> Signup and view all the answers

Consider a signaling pathway where a ligand binds to a receptor, activating a G protein that subsequently stimulates adenylyl cyclase. The resulting increase in cAMP activates PKA, which then phosphorylates and activates a transcription factor, leading to increased gene expression. Which intervention would MOST specifically block this pathway at the level of PKA activation, without directly affecting cAMP production or the activity of other kinases?

<p>Introduction of a specific peptide inhibitor that binds to the PKA catalytic subunit and prevents its activation. (D)</p> Signup and view all the answers

A researcher is studying the effects of ANP on blood pressure. They discover a mutation in the guanylyl cyclase receptor that prevents it from binding to ANP but does not affect its ability to convert GTP to cGMP in vitro. How would this mutation MOST likely affect blood pressure regulation in vivo?

<p>Blood pressure would be abnormally high due to the inability of ANP to activate the receptor. (B)</p> Signup and view all the answers

Consider a renal tubular cell exposed to atrial natriuretic peptide (ANP). Assuming normal cellular physiology, which of the following signaling cascades is MOST directly stimulated, leading to increased sodium excretion?

<p>Activation of guanylyl cyclase, leading to increased cGMP and subsequent activation of protein kinase G (PKG). (D)</p> Signup and view all the answers

A researcher is investigating a novel hormone that binds to a cell-surface receptor with intrinsic tyrosine kinase activity. Following hormone binding, the researcher observes increased phosphorylation of several intracellular proteins. Which of the following mechanisms BEST explains the initial step in this signaling cascade?

<p>The receptor dimerizes and undergoes autophosphorylation on tyrosine residues, creating docking sites for downstream effector proteins. (B)</p> Signup and view all the answers

In a study of patients with suspected endocrine disorders, a subject presents with symptoms indicative of both hyperthyroidism and insulin resistance. Genetic sequencing reveals a mutation affecting the hinge region of a nuclear receptor, impairing its ability to heterodimerize with the retinoid X receptor (RXR). This mutation BEST explains the observed dual pathology through which of the following mechanisms?

<p>Disrupted recruitment of histone acetyltransferases (HATs) to target gene promoters, leading to decreased chromatin accessibility and reduced gene expression. (B)</p> Signup and view all the answers

A researcher is developing a novel therapeutic strategy to treat type 2 diabetes by enhancing insulin sensitivity. Which of the following molecular interventions would MOST directly address the underlying pathophysiology of insulin resistance?

<p>Increasing the expression of the insulin receptor substrate (IRS-1) and enhancing its phosphorylation in response to insulin stimulation. (B)</p> Signup and view all the answers

A researcher is conducting a structure-function analysis of the insulin receptor. They generate a series of mutant receptors, each with a single amino acid substitution in the intracellular tyrosine kinase domain. Which of the following findings would MOST strongly suggest that a particular mutation impairs the receptor's ability to propagate downstream signals?

<p>The mutant receptor fails to undergo autophosphorylation in response to insulin stimulation. (A)</p> Signup and view all the answers

Following prolonged exposure to a synthetic hormone analog, cells exhibit a marked decrease in the number of cell-surface receptors for that hormone, despite continued hormone presence. Which of the following mechanisms BEST explains this phenomenon?

<p>Receptor desensitization via phosphorylation and subsequent binding of arrestins, promoting receptor internalization and degradation. (A)</p> Signup and view all the answers

In a clinical study, researchers are using a sandwich ELISA to quantify levels of a novel cytokine in patient serum samples. After performing the ELISA and obtaining absorbance readings, they observe unexpectedly high background signal across all wells, including those containing only buffer. Which of the following procedural modifications would MOST effectively reduce this background and improve the assay's sensitivity?

<p>Increasing blocking agent concentration in the blocking buffer. (D)</p> Signup and view all the answers

A researcher is investigating the effects of a novel drug on thyroid hormone signaling in vitro. They hypothesize that the drug acts as a selective estrogen receptor modulator (SERM), with tissue-specific effects. Which experimental approach would MOST comprehensively elucidate the drug's mechanism of action on thyroid hormone-responsive genes?

<p>Conducting chromatin immunoprecipitation followed by sequencing (ChIP-Seq) to identify genome-wide changes in transcription factor binding at thyroid hormone response elements (TREs). (D)</p> Signup and view all the answers

Given the established mechanisms of steroid hormone action, which of the following scenarios would MOST effectively disrupt estrogen-mediated gene transcription in a breast cancer cell line, assuming all interventions are equally achievable?

<p>Stable transfection of the cells with a dominant-negative mutant of the estrogen receptor (ER) that retains its DNA-binding domain but lacks the ability to recruit co-activators. (B)</p> Signup and view all the answers

Considering the intricate interplay between hormone response elements (HREs) and transcription factors (TFs), which of the following experimental designs would be MOST suitable for identifying novel co-repressors that modulate estrogen receptor (ER) activity at a specific HRE within the promoter region of the MYC gene?

<p>A DNA affinity purification assay using an oligonucleotide corresponding to the <em>MYC</em> HRE as bait, followed by mass spectrometry to identify associated proteins and validation using siRNA knockdown experiments. (C)</p> Signup and view all the answers

Given the complexity of steroid hormone receptor dimerization, specifically concerning homodimers and heterodimers, what is the functional significance of leucine zipper motifs found in many nuclear receptors?

<p>Leucine zipper motifs mediate protein-protein interactions, essential for dimerization and subsequent binding to hormone response elements on DNA. (A)</p> Signup and view all the answers

In the context of Group 2 hormone signaling (hydrophilic), how would a mutation that disrupts the GTPase activity of a Gαs subunit MOST likely affect downstream signaling events?

<p>It would cause constitutive activation of the Gαs subunit, resulting in sustained activation of adenylyl cyclase and elevated levels of cAMP. (A)</p> Signup and view all the answers

Considering the diverse mechanisms by which nuclear receptor proteins (transcription factors) modulate gene expression, which of the following scenarios would MOST effectively enhance the transcriptional activity of an estrogen receptor (ER) homodimer bound to an estrogen response element (ERE)?

<p>Recruitment of co-activator proteins possessing histone acetyltransferase (HAT) activity to the promoter region, leading to chromatin decondensation. (B)</p> Signup and view all the answers

Suppose a novel synthetic estrogen analog is developed that exhibits significantly higher binding affinity for the estrogen receptor (ER) but fails to induce a conformational change necessary for co-activator recruitment. What is the most likely functional consequence of administering this analog to cultured cells?

<p>Complete ablation of ER-mediated gene transcription as the analog acts as a potent ER antagonist. (C)</p> Signup and view all the answers

Assume a researcher is investigating the tissue-specific effects of estrogen signaling. They discover that a particular cell type expresses a novel variant of the estrogen receptor (ER) that lacks the DNA-binding domain but retains the ability to interact with estrogen and other transcription factors. How might this variant MOST likely influence estrogen-dependent gene expression in that cell type?

<p>It could modulate the activity of other transcription factors by forming non-DNA-binding complexes, thereby indirectly influencing estrogen-responsive genes. (D)</p> Signup and view all the answers

In the context of hormone signaling, consider a cell line engineered to express both a functional estrogen receptor (ER) and a constitutively active phosphodiesterase that rapidly degrades cAMP. How would the simultaneous stimulation of these cells with both estrogen and a Group 2 hormone that signals through cAMP affect gene expression, relative to stimulation with each hormone alone?

<p>Estrogen-responsive genes would be upregulated, while cAMP-responsive genes would be suppressed due to the action of the phosphodiesterase. (A)</p> Signup and view all the answers

Consider a scenario where a novel synthetic analogue of a hormone exhibits significantly prolonged activity compared to its endogenous counterpart. Which of the following mechanisms, related to hormone delivery and clearance, is LEAST likely to contribute to this extended duration of action?

<p>Increased dissociation constant with transport proteins, leading to a higher concentration of free, biologically active hormone in circulation. (D)</p> Signup and view all the answers

A researcher is investigating a newly discovered cell signaling pathway activated by a peptide hormone. Initial findings suggest that the hormone's receptor lacks intrinsic kinase activity but triggers a rapid and transient increase in intracellular calcium levels. Based on this information, which of the following receptor mechanisms is MOST likely involved?

<p>Direct activation of a G protein-coupled receptor (GPCR) that stimulates phospholipase C (PLC) activity, leading to inositol trisphosphate (IP3) production and subsequent calcium release from the endoplasmic reticulum. (C)</p> Signup and view all the answers

In the context of endocrine disruption, certain synthetic chemicals can mimic or antagonize the effects of endogenous hormones. Given the different classes of hormones and their mechanisms of action, which of the following scenarios would pose the GREATEST risk of widespread and long-lasting physiological effects?

<p>Chronic exposure to a lipophilic chemical that acts as an agonist for a nuclear receptor, influencing gene transcription in multiple tissues. (D)</p> Signup and view all the answers

A novel therapeutic strategy aims to selectively modulate hormone action in a tissue-specific manner. Which of the following approaches would be MOST effective in achieving this targeted modulation, minimizing off-target effects in other tissues?

<p>Developing a pro-hormone that is converted into the active hormone only in specific tissues expressing the required activating enzymes. (D)</p> Signup and view all the answers

In the context of hormone action and cellular signaling, which of the following scenarios would MOST likely result in a complete and irreversible abrogation of a cell's ability to respond to a specific hormone?

<p>Genetic mutation causing complete deletion of the gene encoding the hormone receptor protein. (C)</p> Signup and view all the answers

A researcher discovers a novel hormone that, despite being lipophilic, readily dissolves in aqueous solutions and does not require a transport protein in the bloodstream. Furthermore, it directly binds to a cell surface receptor. Which of the following modifications to the established classification of hormones would this discovery necessitate?

<p>Eliminating the clear distinction between lipophilic and hydrophilic hormones based on their solubility and transport mechanisms. (C)</p> Signup and view all the answers

A pharmaceutical company is developing a drug that aims to modulate the 'fight or flight' response by targeting specific hormone receptors. Considering the hormones involved in this response and their diverse receptor subtypes, which strategy would MOST effectively mitigate unintended cardiovascular side effects?

<p>Designing a highly selective beta-3 adrenergic receptor agonist to promote lipolysis and increase energy availability without significantly impacting cardiac function. (D)</p> Signup and view all the answers

A patient presents with symptoms indicative of hormone resistance, where target cells fail to respond appropriately to a specific hormone despite normal hormone levels. Assuming this resistance is NOT due to a receptor mutation, which of the following mechanisms is the LEAST likely cause?

<p>Reduced rate of hormone synthesis and secretion, leading to insufficient hormone concentrations reaching target tissues. (D)</p> Signup and view all the answers

Consider a novel synthetic hormone analog that exhibits both high hydrophobicity and an unusually large molecular weight, impeding its diffusion across cell membranes. Which of the following mechanisms is MOST likely to mediate its cellular signaling?

<p>Interaction with a cell-surface receptor coupled to a G protein, initiating a second messenger cascade. (D)</p> Signup and view all the answers

A researcher discovers a cell line that is unresponsive to a known lipophilic hormone, despite the presence of functional hormone receptors within the cytoplasm. Furthermore, mRNA expression for downstream targets of that hormone is normal. The most probable cause of hormone resistance in this cell line is:

<p>Impairment in the nuclear translocation machinery, preventing the hormone-receptor complex from entering the nucleus. (C)</p> Signup and view all the answers

In a cell line engineered to express both a cell-surface receptor for a hydrophilic hormone and an intracellular receptor for a lipophilic hormone. Which of the following scenarios would MOST selectively disrupt signaling by the lipophilic hormone?

<p>Selective knockdown of importin-β, a protein essential for nuclear import. (D)</p> Signup and view all the answers

A patient presents with a syndrome characterized by resistance to multiple lipophilic hormones, despite normal hormone levels and receptor expression. Whole-exome sequencing reveals a mutation in a novel gene, the product of which is ubiquitously expressed and localizes to the endoplasmic reticulum (ER). This gene MOST likely encodes a protein involved in:

<p>Facilitating the proper folding and modification of intracellular hormone receptors. (B)</p> Signup and view all the answers

A researcher is studying the effects of a novel synthetic lipophilic hormone that, unlike natural hormones, does not bind to plasma proteins in the circulation. Compared to a natural lipophilic hormone with similar potency, the synthetic hormone would likely exhibit:

<p>A significantly shorter half-life in the circulation and a more rapid onset of action. (C)</p> Signup and view all the answers

In a cell lacking functional aquaporins, how would the signaling pathway of a hydrophilic hormone that activates a G protein-coupled receptor (GPCR) be affected, assuming the GPCR's signaling cascade involves changes in intracellular osmolarity?

<p>The signaling cascade would be attenuated due to impaired water movement and altered intracellular osmolarity adjustments. (A)</p> Signup and view all the answers

A researcher identifies a novel mutation in a cell-surface receptor that normally binds a hydrophilic hormone. This mutation causes the receptor to constitutively aggregate into large clusters within lipid rafts. What is the MOST likely effect on hormone signaling?

<p>Disrupted interaction with downstream signaling proteins, leading to impaired signal transduction. (C)</p> Signup and view all the answers

A particular endocrine disrupting chemical (EDC) is found to non-competitively inhibit the binding of a lipophilic hormone to its intracellular receptor. Further analysis reveals that EDC binds to a region of the receptor distinct from the hormone-binding domain, inducing a conformational change that reduces receptor's affinity for DNA. Which of the following best describes EDC's mechanism of action?

<p>Allosteric antagonism, where the EDC binding alters the receptor's structure, diminishing its DNA-binding affinity. (D)</p> Signup and view all the answers

Consider a researcher investigating the impact of synthetic hormone analogs on cellular function. They observe that a specific analog, unlike the naturally occurring hormone, induces a sustained and amplified signal even after the initial stimulus is removed. Which of the following mechanisms BEST explains this phenomenon, assuming the analog interacts with the same receptor as the natural hormone?

<p>The analog induces epigenetic modifications at the promoter region of genes encoding negative feedback regulators, suppressing their expression and preventing signal attenuation. (C)</p> Signup and view all the answers

A novel endocrine disruptor is discovered that preferentially accumulates in lipid bilayers. Given this characteristic, which of the following mechanisms is MOST likely to be directly affected by this disruptor?

<p>Alteration of the diffusion dynamics of transmembrane hormone receptors within the plasma membrane, affecting their ability to form functional dimers or oligomers. (C)</p> Signup and view all the answers

In a cell line engineered to express a chimeric receptor consisting of the extracellular domain of a growth factor receptor and the intracellular domain of a steroid hormone receptor, what would be the MOST likely outcome following exposure to the growth factor?

<p>Translocation of the chimeric receptor to the nucleus and modulation of gene transcription through hormone response elements. (A)</p> Signup and view all the answers

A research team identifies a novel mutation in the gene encoding a hormone receptor. This mutation results in a receptor protein that exhibits constitutive activity, even in the absence of hormone binding. Which of the following therapeutic strategies would be the MOST effective in counteracting the effects of this constitutively active receptor?

<p>Targeting the mutant receptor for degradation using a proteolysis-targeting chimera (PROTAC) molecule that recruits an E3 ubiquitin ligase. (B)</p> Signup and view all the answers

A researcher is studying a cell line that exhibits resistance to a Group 2 hormone. Despite normal receptor expression and ligand binding, the downstream signaling cascade is significantly attenuated. Through phosphoproteomic analysis, they discover a marked increase in the phosphorylation of a specific protein phosphatase. Which of the following is the MOST likely explanation for the observed hormone resistance?

<p>The increased phosphatase activity dephosphorylates and inactivates key signaling intermediates in the hormone response pathway, disrupting signal propagation. (A)</p> Signup and view all the answers

A scientist is investigating the mechanism by which a novel synthetic hormone analog selectively activates a specific subset of genes regulated by a steroid hormone receptor. Chromatin immunoprecipitation sequencing (ChIP-Seq) reveals that, unlike the natural hormone, the analog promotes receptor binding to a distinct set of hormone response elements (HREs) located in intergenic regions far from known gene promoters. Which of the following models BEST explains this observation?

<p>The analog enhances the interaction of the receptor with specific long non-coding RNAs (lncRNAs) that guide the receptor to distal genomic sites through RNA-DNA interactions. (C)</p> Signup and view all the answers

A researcher is studying the effects of chronic exposure to a low-dose endocrine disruptor on hormone signaling in a population of cells. They observe that while the initial hormone response is normal, prolonged exposure leads to a progressive desensitization of the cells, characterized by a reduced amplitude and duration of the downstream signaling cascade. Which of the following mechanisms is the LEAST likely to contribute to this desensitization?

<p>Accumulation of constitutively active G proteins that continuously stimulate downstream signaling pathways, leading to receptor-independent activation. (A)</p> Signup and view all the answers

In the context of hormone signaling, consider a scenario where a cell simultaneously receives signals from both a Group 1 (lipophilic) and a Group 2 (hydrophilic) hormone. Assuming both hormones act on the same target gene, which of the following mechanisms would allow for synergistic or antagonistic interactions between the two signaling pathways at the level of transcription?

<p>Competition for limiting amounts of shared co-activator or co-repressor proteins that are required for both Group 1 and Group 2 hormone-mediated transcriptional regulation. (B)</p> Signup and view all the answers

A pharmaceutical company is developing a novel drug that aims to selectively modulate the activity of a specific hormone receptor isoform without affecting other isoforms of the same receptor. Which of the following approaches would be MOST promising in achieving this isoform selectivity?

<p>Creating a small molecule that selectively interacts with a unique regulatory domain or post-translational modification site present only on the target receptor isoform. (D)</p> Signup and view all the answers

Consider a scenario where a cell is exposed to a constant concentration of a hormone over an extended period. Initially, the cell exhibits a robust response, but over time, the response gradually diminishes despite the continued presence of the hormone. This phenomenon is known as desensitization or adaptation. Which of the following mechanisms is LEAST likely to contribute to this desensitization process?

<p>Increased hormone synthesis: The cell compensates for the prolonged hormone exposure by increasing its own hormone synthesis, leading to an amplified response. (B)</p> Signup and view all the answers

A researcher discovers a novel mutation in the gene encoding a G protein-coupled receptor (GPCR) that results in constitutive receptor activation, even in the absence of its cognate ligand. Which of the following mechanisms is the MOST plausible explanation for this constitutive activity?

<p>The mutation stabilizes the receptor in an active conformation by mimicking the conformational changes induced by ligand binding. (C)</p> Signup and view all the answers

A research team is investigating the effects of a novel synthetic glucocorticoid on gene expression in a human cell line. They observe that while the synthetic glucocorticoid effectively induces the expression of some glucocorticoid-responsive genes, it fails to induce the expression of others. Which of the following mechanisms is the MOST likely explanation for this selective gene regulation?

<p>The synthetic glucocorticoid promotes the recruitment of distinct sets of co-activator and co-repressor proteins to different glucocorticoid response elements (GREs), leading to selective gene regulation. (D)</p> Signup and view all the answers

Consider a signaling pathway initiated by a hormone binding to its receptor, leading to the activation of a cascade of kinases. A researcher discovers that a specific scaffolding protein is essential for the efficient and specific activation of this pathway. Which of the following is the MOST likely mechanism by which this scaffolding protein facilitates signaling?

<p>By physically bringing together specific kinases and their substrates, thereby increasing the efficiency and specificity of phosphorylation events. (D)</p> Signup and view all the answers

A scientist is studying the effects of a novel mutation in the ligand-binding domain of a nuclear hormone receptor. This mutation alters the receptor's affinity for its cognate hormone and also affects its ability to interact with co-regulatory proteins. Which of the following experimental approaches would be the MOST suitable for characterizing the functional consequences of this mutation on receptor activity?

<p>Employing a combination of radioligand binding assays, ChIP assays, and luciferase reporter assays to comprehensively assess the effects of the mutation on receptor function. (A)</p> Signup and view all the answers

A researcher is investigating the role of hormone receptor trafficking in regulating hormone signaling. They discover that a specific E3 ubiquitin ligase is responsible for ubiquitinating a hormone receptor, leading to its internalization and degradation. Which of the following mechanisms is the MOST likely way in which this ubiquitination regulates hormone signaling?

<p>By targeting the receptor for degradation via the proteasome or lysosome pathway, thereby reducing the number of receptors available for signaling. (C)</p> Signup and view all the answers

Flashcards

Fight or Flight Response

A physiological reaction triggered by a perceived threat, leading to increased blood flow and energy release.

Hormone Delivery Factors

Factors impacting how effectively hormones reach their target cells, including synthesis rate and proximity.

Hormone Classification

Hormones categorized by their chemical nature, solubility, and receptor interaction.

Steroid Hormones

Hormones derived from cholesterol, hydrophobic, and transported in blood bound to proteins.

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Peptide Hormones

Short chains of amino acids that act as hormones, such as insulin.

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Amine Hormones

Hormones derived from amino acids, including adrenaline, which affect various bodily responses.

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Hydrophilic Hormones

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

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Receptor Status

The condition and number of receptors available to bind hormones, affecting cellular response.

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Water-soluble hormones

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

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Lipid-soluble hormones

Hormones that can diffuse through cell membranes to reach intracellular receptors.

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Extracellular receptors

Receptors located on the cell membrane for signaling from water-soluble hormones.

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Intracellular receptors

Receptors located in the cytosol or nucleus for lipid-soluble hormones.

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Second messenger

Molecule that carries the signal inside cells after binding of water-soluble hormones.

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Signal cascade

Series of events triggered by water-soluble hormones leading to a cellular response.

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Transport proteins

Proteins that bind to hydrophobic hormones for circulation in the blood.

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Hormones

Biochemical messengers released by endocrine glands that impact gene expression.

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Endocrine vs Nervous System

Endocrine system uses hormones for slow, long-lasting effects; nervous system uses electrical signals for fast responses.

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Feedback Mechanisms

Processes where hormone levels are regulated by the product affecting its own production.

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Paracrine Signalling

Type of hormone signalling where target cells are nearby the secreting cells.

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Autocrine Signalling

Type of hormone signalling where the target cell is also the secreting cell.

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Hormone Specificity

Hormones act on specific target cells through their respective receptors.

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Hormonal Actions

Changes in cell conditions due to hormone binding, affecting permeability, protein expression, or enzyme activity.

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Hypothalamus

Master endocrine gland that regulates various hormone-producing glands.

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Insulin

Hormone that decreases blood sugar by promoting glucose uptake by cells.

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Thyroxine

Hormone that regulates the body's basal metabolic rate.

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Adrenaline

Hormone that stimulates the 'fight or flight' response during stress.

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Negative Feedback Loop

A regulation process where increased hormone levels inhibit further production.

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Positive Feedback Loop

A mechanism that amplifies hormone production in response to an initial stimulus.

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Phosphorylation

A process where a phosphate group is added to proteins, modifying their function and activity.

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cAMP

Cyclic AMP, a second messenger that transmits hormone signals within cells.

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PKA

Protein Kinase A, an enzyme activated by cAMP that phosphorylates various proteins.

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Ephedrine response

Process initiated by hormones (like epinephrine) that triggers metabolic activities.

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Phosphodiesterases

Enzymes that deactivate cAMP, providing negative feedback in signaling pathways.

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IP3

Inositol trisphosphate, a second messenger that triggers calcium release in cells.

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Calmodulin

A calcium-binding protein that regulates protein kinases when bound with calcium.

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cGMP

Cyclic GMP, a second messenger involved in various physiological processes, independent of GPCRs.

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cGMP Function

cGMP activates protein kinase G (PKG) and regulates ion channels.

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Insulin Receptor Structure

Insulin receptor is a tetramer and a receptor tyrosine kinase.

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Autophosphorylation

Insulin receptors phosphorylate each other at tyrosine residues after ligand binding.

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Insulin Signaling

Phosphorylated tyrosines serve as binding sites for IRS-1 to propagate signals.

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Type 2 Diabetes Cause

Insulin receptor insensitivity leads to reduced signaling and high blood glucose.

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Graves' Disease

Autoantibodies against TSH receptor cause increased thyroid hormone production (hyperthyroidism).

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ELISA Purpose

Enzyme-linked immunosorbent assay uses antibodies for target detection and quantification.

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Sandwich ELISA

Involves coating wells with antibodies to capture hormones or antigens from samples.

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Hormone-Receptor Complex

A complex formed when a hormone binds to its receptor, initiating a cellular response.

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Hormone Response Elements (HREs)

Regions of DNA that contain a consensus sequence for binding activated hormone receptors.

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Steroid Hormone Action

Steroid hormones cross the cell membrane and bind to intracellular receptors to exert their effects.

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G-Protein-Coupled Receptors (GPCRs)

Receptors on cell membranes that activate G-proteins upon hormone binding to propagate signals.

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Protein Kinase A (PKA)

An enzyme activated by cAMP that plays a crucial role in various signaling pathways.

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Consensus Sequence

A specific sequence of DNA recognized by proteins, including hormone receptors, for binding.

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Intracellular Signaling

The process by which signals from receptors are transmitted into the cell to initiate a response.

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Study Notes

Cellular Mechanisms of Hormone Action

  • Hormones play a fundamental role in the human body, coordinating slow-acting responses vital for reproduction, development, metabolism, growth, and behavior.
  • Hormones are biochemical messengers released by endocrine glands impacting gene expression and protein states.
  • Hormones complement neurotransmitters, functioning as widespread messengers.
  • Hormones are classified by their chemical nature (steroids, peptides, glycoproteins) and solubility (hydrophilic vs. hydrophobic).
  • Solubility influences the pathway by which the hormone acts on the target cell.
  • Hydrophobic hormones (Group 1) readily diffuse through the cell membrane and bind to intracellular receptors, influencing gene transcription.
  • Hydrophilic hormones (Group 2) bind to cell surface receptors, initiating a second messenger cascade to amplify the signal.
  • Defects in hormone receptors can cause diseases, including type 2 diabetes due to insensitivity of receptors and Graves' disease, caused by autoimmune binding to receptors.

Learning Objectives

  • Describe basic roles and mechanisms of action of hormones.
  • Differentiate between lipophilic and hydrophilic hormone groups.
  • Distinguish how Group 1 and Group 2 hormones affect cellular states.
  • Explain how steroid hormones utilize hormone response elements (HREs) to regulate gene expression.
  • Describe how hydrophilic hormone signaling uses second messenger cascades for amplification.
  • Explain how defects in hormone responses and receptors can cause disease.
  • Describe how ELISA (Enzyme-linked Immunosorbent Assay) is used to measure hormone levels.
  • Understand how the endocrine system regulates hormone production via negative and positive feedback mechanisms.

Two Systems Coordinate Communication

  • The endocrine system regulates slower, long-term responses through hormone secretion.
  • The nervous system facilitates rapid electrical signaling through neurons.

The Endocrine System Secretes Hormones

  • Hormones are chemical messengers.
  • Endocrine glands secrete hormones into the bloodstream.
  • Hormones regulate gene expression and protein states.
  • Hormones and neurotransmitters work together to influence bodily functions.

Regulation within the Endocrine System

  • Most hormones are regulated by feedback mechanisms.
  • Negative feedback loops maintain a narrow range of hormone concentrations.
  • Positive feedback reinforces initial stimulus to amplify hormone production.

Hormonal Signaling

  • Endocrine signaling typically involves hormones acting on distant target cells.
  • Paracrine signaling involves target cells near the secreting cells, while autocrine signaling occurs when the target cell is the secreting cell.

Hormones: Highly Selective and Potent

  • Hormones exhibit high selectivity and potency due to specific receptors.
  • Cells express receptors specific to different hormones.

Hormones: Basic Principles

  • Endocrine glands receive and process stimuli, secreting hormones into the bloodstream to target tissues.
  • Hormone receptors on target tissues bind hormones with high specificity.
  • Hormone action modulates cellular conditions via various mechanisms.

Endocrine System: General Functions

  • The presentation outlines the roles of various endocrine glands and their associated hormones.
  • It covers hormones related to growth, metabolism, circulatory/digestive systems, immunity, and reproduction.

ELISA (Enzyme-Linked Immunosorbent Assay)

  • ELISA utilizes antibodies for specific hormone detection.
  • ELISA methods include direct, indirect, sandwich, and competitive ELISAs.
  • ELISA allows for quantitative or qualitative hormone measurement in samples.

Classification of Hormones and hormone structure

  • Hormones are classified based on diverse criteria including chemical nature (steroids, peptides, etc.) solubility (hydrophobic/hydrophilic)
  • These differences directly impact how the body distributes and utilizes those hormones.
  • Hormones differ in both structure and function.

Steps in Group 1 Hormone (Hydrophobic) Intracellular Signaling

  • Hydrophobic hormones readily diffuse through cell membranes.
  • These hormones bind to intracellular receptors within the cell.
  • The hormone-receptor complex translocates to the nucleus, binding hormone response elements on DNA.

Steps in Group 2 Hormone (Hydrophilic) Signaling

  • Hydrophilic hormones bind to cell surface receptors.
  • Activated receptors trigger intracellular signaling pathways.
  • Second messengers amplify the signal.

Other Second Messengers

  • G-proteins can activate processes using IP3/calcium or cGMP pathways.

Hormone Receptors with Protein Kinase Activity

  • Insulin receptors show a tetrameric structure.
  • These receptors phosphorylate each other following ligand binding.
  • Phosphorylation initiates signal transduction.

Hormones Drive Biological Processes

  • Hormones regulate many biological processes within the body.
  • Cells respond to many hormones simultaneously.

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Examine GPCR signaling pathways, calcium release, and the impact of mutations on receptor activation. Investigate interventions to inhibit calcium release and the effects on vascular smooth muscle cells. Explore cGMP signaling and its role in hypertension treatment.

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