hormone receptors Flashcards
list some hormones that can be described as water soluble
- adrenaline
- insulin
- glucagon
- vasopressin
- ACTH
- TSH
- melatonin
discuss the pathway of water soluble hormones interacting with cell surface receptors and triggering internal signalling events
- Hormone Secretion: Water-soluble hormones are typically secreted into the bloodstream by endocrine glands in response to various stimuli.
- Circulation: Once released into the bloodstream, water-soluble hormones travel throughout the body, reaching target cells that express specific receptors for these hormones.
- Receptor Binding: Upon reaching the target cell, the water-soluble hormone binds to its specific receptor located on the outer surface of the cell membrane. These receptors are often transmembrane proteins, which span the lipid bilayer of the cell membrane.
- Conformational Change: Hormone binding induces a conformational change in the receptor protein. This change in shape activates the receptor, initiating a cascade of intracellular signaling events.
- Activation of Intracellular Signaling Pathways: The activated receptor acts as a molecular switch, initiating intracellular signaling cascades through various mechanisms.
- Activation of Second Messengers: The activated G protein then triggers the production or release of second messenger molecules within the cell. Common second messengers include cyclic adenosine monophosphate (cAMP), inositol trisphosphate (IP3), and diacylglycerol (DAG). These second messengers serve as signaling intermediates that relay the hormonal signal from the cell surface to intracellular targets.
- Cellular Response: The second messengers, in turn, activate or inhibit downstream effector molecules such as protein kinases, ion channels, or transcription factors, depending on the specific signaling pathway and target cell type. This leads to various cellular responses, such as changes in gene expression, alterations in enzyme activity, or modulation of ion fluxes across the cell membrane.
- Termination of Signal: To prevent sustained cellular responses, the signaling cascade is tightly regulated. This can occur through mechanisms such as receptor desensitization, internalization, or enzymatic degradation of second messengers.
which hormones exclusively use the adenyl cyclase pathway
- calcitonin
- PTH
- glucagon
- CRH
- somatostatin
- ACTH
- TSH
- FSH
- Adrenaline
which hormones exclusively use the phospholipase C pathway
- GnTH
- oxytocin
- TRH
- Vasopressin
which hormones exclusively use the tyrosine kinase pathway
insulin
which signal transductions system does atrial natriuretic peptide use
guanylyl cyclase signaling pathway
what are the actions of ANP
vasodilation
which signal molecule does ANP use
cGMP
provide a detailed description of the tyrosine kinase receptor signalling pathway using insulin receptor as an example
Insulin Binding: Insulin, a peptide hormone produced by the pancreas, binds to its specific receptor, the insulin receptor (IR), which is a transmembrane protein
Receptor Activation: Insulin binding induces conformational changes in the insulin receptor, leading to autophosphorylation of specific tyrosine residues within the intracellular domain. Autophosphorylation activates the intrinsic tyrosine kinase activity of the receptor.
Recruitment of Insulin Receptor Substrate (IRS): Activated insulin receptors phosphorylate tyrosine residues on insulin receptor substrate (IRS) proteins which serve as docking proteins for downstream signaling molecules.
Activation of Phosphoinositide 3-Kinase (PI3K) Pathway: IRS proteins recruit and activate phosphoinositide 3-kinase (PI3K)
Activation of Protein Kinase B (Akt): PIP3 recruits Akt
Akt-Mediated Cellular Responses: Akt phosphorylates and regulates various downstream targets
- Akt phosphorylates and inhibits glycogen synthase kinase 3 (GSK-3), leading to glycogen synthesis and inhibition of glycogen breakdown.
- Akt promotes glucose uptake
- Akt stimulates protein synthesis
- Akt inhibits apoptosis
Termination of Signal: The insulin signaling pathway is tightly regulated to prevent sustained activation. Phosphatases, such as phosphatase and tensin homolog (PTEN), dephosphorylate PIP3, attenuating Akt activation. Additionally, IRS proteins can be negatively regulated by serine phosphorylation, leading to their degradation.
list lipid soluble proteins
- cortisol
- testosterone
- estrogen
- progesterone
- Thyroxine (T4) and
- Triiodothyronine (T3)
describe how cortisol affects the cell upon its arrival
- Diffusion Across the Cell Membrane: Cortisol is lipid-soluble, allowing it to easily diffuse across the cell membrane without the need for specific transporters.
- Binding to Glucocorticoid Receptors (GRs): Once inside the cell, cortisol binds to cytoplasmic glucocorticoid receptors (GRs)
- Activation of Glucocorticoid Receptors: Cortisol binding induces a conformational change in the glucocorticoid receptor, causing it to activate
- Transcriptional Regulation: Within the nucleus, the cortisol-GR complex acts as a transcription factor, directly influencing gene expression by binding to specific DNA sequences known as glucocorticoid response elements (GREs) located in the promoter regions of target genes.
- Regulation of Gene Expression: Binding of the cortisol-GR complex to GREs can have several effects on gene expression:
- Activation of Transcription: In some cases, cortisol-GR binding leads to the activation of target genes, resulting in increased mRNA synthesis.
- Repression of Transcription: In other cases, cortisol-GR binding may suppress the transcription of target genes, leading to decreased mRNA synthesis. - Diverse Physiological Effects: Through its actions on gene expression, cortisol regulates the expression of a wide range of genes involved in various physiological processes, including:
- Metabolism
- Immune Function
- Stress Response
- Development and Growth - Feedback Regulation: Cortisol levels are tightly regulated through a negative feedback mechanism involving the hypothalamic-pituitary-adrenal (HPA) axis. Elevated cortisol levels inhibit the release of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH), leading to decreased cortisol synthesis and secretion, thereby maintaining homeostasis.
what are response elements
specific DNA sequences within the promoter or enhancer regions of genes that serve as binding sites for hormone receptors or transcription factors activated by hormonal signaling pathways. These response elements play a crucial role in mediating the effects of hormones on gene expression
what are the RAS-oncongene and why are they important from a clinical perspective
RAS oncogenes refer to a family of genes that encode proteins involved in cell signaling pathways regulating cell growth, differentiation, and survival.
clinical implications:
- cancer development
- prognostic marker
- target for therapy
- biomarker for percision medicine
are there differences in the time that it takes hormones to exert their actions on target cells? are water soluble or lipid soluble hormones faster and why
yes:
- chmical nature of hormone (water vs lipid soluble)
- mechanism of action
- downstream signalling pathways involved
generally water soluble hormones tend to exert their effets more rapidly compared to lipid soluble:
- water soluble are hydrophilic and can readily dissolve in the blood stream, whereas lipid needs carrier proteins
- water soluble usually bind to cell surface receptors on the outer membrane, whereas lipid diffuse across the membrane (takes longer to translocate into the nucleus)
- water often exert their effects through second messenger systems which amplify the signal, lipid directly influence the gene transcription which can take longer
- water have shorter duration of action
