1 / 54

LECTURE 2 Mechanism of Hormone Action

LECTURE 2 Mechanism of Hormone Action. Nabil Bashir 2009. Mechanism of Hormone Action. Hormones produce one or more of the following cellular changes in target cells Alter plasma membrane permeability Stimulate protein synthesis Activate or deactivate enzyme systems

uriel-oneil
Download Presentation

LECTURE 2 Mechanism of Hormone Action

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. LECTURE 2Mechanism of Hormone Action Nabil Bashir 2009

  2. Mechanism of Hormone Action • Hormones produce one or more of the following cellular changes in target cells • Alter plasma membrane permeability • Stimulate protein synthesis • Activate or deactivate enzyme systems • Induce secretory activity • Stimulate mitosis

  3. Structure of Cell Surface Receptors Cell surface receptors are integral membrane proteins and, as such, have regions that contribute to three basic domains: • Extracellular domains: Some of the residues exposed to the outside of the cell interact with and bind the hormone - another term for these regions is the ligand-binding domain. • Transmembrane domains: Hydrophobic stretches of amino acids and serve to anchor the receptor in the membrane. • Cytoplasmic or intracellular domains: Tails or loops of the receptor that are within the cytoplasm react to hormone binding by interacting in some way with other molecules, leading to generation of second messengers. Cytoplasmic residues of the receptor are thus the effector region of the molecule.

  4. Amino Acid-Based Hormone Action: cAMP Second Messenger • Hormone (first messenger) binds to its receptor, which then binds to a G protein • The G protein is then activated as it binds GTP, displacing GDP • Activated G protein activates the effector enzyme adenylate cyclase • Adenylate cyclase generates cAMP (second messenger) from ATP • cAMP activates protein kinases, which then cause cellular effects

  5. Amino Acid-Based Hormone Action: cAMP Second Messenger Extracellular fluid Hormone A Adenylate cyclase Hormone B 1 1 2 3 3 2 GTP GTP GTP GTP 4 Receptor Receptor Gs Gi GDP GDP GTP GTP ATP cAMP Catecholamines ACTH FSH LH Glucagon PTH TSH Calcitonin 5 Triggers responses of target cell (activates enzymes, stimulates cellular secretion, opens ion channels, etc.) Inactive protein kinase A Active protein kinase A Cytoplasm Figure 16.2

  6. Amino Acid-Based Hormone Action: cAMP Second Messenger Extracellular fluid Hormone A Adenylate cyclase Receptor Gs Catecholamines ACTH FSH LH Glucagon PTH TSH Calcitonin Cytoplasm Figure 16.2

  7. Amino Acid-Based Hormone Action: cAMP Second Messenger Extracellular fluid Hormone A Adenylate cyclase 1 Receptor Gs Catecholamines ACTH FSH LH Glucagon PTH TSH Calcitonin Cytoplasm Figure 16.2

  8. Amino Acid-Based Hormone Action: cAMP Second Messenger Extracellular fluid Hormone A Adenylate cyclase 1 2 GTP Receptor Gs GDP GTP Catecholamines ACTH FSH LH Glucagon PTH TSH Calcitonin Cytoplasm Figure 16.2

  9. Amino Acid-Based Hormone Action: cAMP Second Messenger Extracellular fluid Hormone A Adenylate cyclase 1 2 3 GTP GTP Receptor Gs GDP GTP Catecholamines ACTH FSH LH Glucagon PTH TSH Calcitonin Cytoplasm Figure 16.2

  10. Amino Acid-Based Hormone Action: cAMP Second Messenger Extracellular fluid Hormone A Adenylate cyclase 1 2 3 GTP GTP 4 Receptor Gs GDP GTP ATP cAMP Catecholamines ACTH FSH LH Glucagon PTH TSH Calcitonin Cytoplasm Figure 16.2

  11. Amino Acid-Based Hormone Action: cAMP Second Messenger Extracellular fluid Hormone A Adenylate cyclase 1 2 3 GTP GTP 4 Receptor Gs GDP GTP ATP cAMP Catecholamines ACTH FSH LH Glucagon PTH TSH Calcitonin 5 Triggers responses of target cell (activates enzymes, stimulates cellular secretion, opens ion channels, etc.) Inactive protein kinase A Active protein kinase A Cytoplasm Figure 16.2

  12. Amino Acid-Based Hormone Action: cAMP Second Messenger Extracellular fluid Adenylate cyclase Hormone B Receptor Gi Catecholamines ACTH FSH LH Glucagon PTH TSH Calcitonin Cytoplasm Figure 16.2

  13. Amino Acid-Based Hormone Action: cAMP Second Messenger Extracellular fluid Adenylate cyclase Hormone B 1 Receptor Gi Catecholamines ACTH FSH LH Glucagon PTH TSH Calcitonin Cytoplasm Figure 16.2

  14. Amino Acid-Based Hormone Action: cAMP Second Messenger Extracellular fluid Adenylate cyclase Hormone B 1 2 GTP Receptor Gi GDP GTP Catecholamines ACTH FSH LH Glucagon PTH TSH Calcitonin Cytoplasm Figure 16.2

  15. Amino Acid-Based Hormone Action: cAMP Second Messenger Extracellular fluid Adenylate cyclase Hormone B 1 3 2 GTP GTP Receptor Gi GDP GTP Catecholamines ACTH FSH LH Glucagon PTH TSH Calcitonin Cytoplasm Figure 16.2

  16. Amino Acid-Based Hormone Action: cAMP Second Messenger Extracellular fluid Hormone A Adenylate cyclase Hormone B 1 1 2 3 3 2 GTP GTP GTP GTP 4 Receptor Receptor Gs Gi GDP GDP GTP GTP ATP cAMP Catecholamines ACTH FSH LH Glucagon PTH TSH Calcitonin 5 Triggers responses of target cell (activates enzymes, stimulates cellular secretion, opens ion channels, etc.) Inactive protein kinase A Active protein kinase A Cytoplasm Figure 16.2

  17. Amino Acid-Based Hormone Action: PIP-Calcium • Hormone binds to the receptor and activates G protein • G protein binds and activates phospholipase • Phospholipase splits the phospholipid PIP2 into diacylglycerol (DAG) and IP3 (both act as second messengers) • DAG activates protein kinases; IP3 triggers release of Ca2+ stores • Ca2+ (third messenger) alters cellular responses

  18. Amino Acid-Based Hormone Action: PIP Mechanism Extracellular fluid Hormone DAG 1 4 5 Active protein kinase C 2 3 PIP2 GTP GTP Receptor Gq Inactive protein kinase C GDP GTP IP3 Phospholipase C Catecholamines TRH ADH GnRH Oxytocin Triggers responses of target cell 5 Endoplasmic reticulum 6 Cytoplasm Ca2+ Ca2+- calmodulin Figure 16.3

  19. Amino Acid-Based Hormone Action: PIP Mechanism Extracellular fluid Hormone Receptor Gq Catecholamines TRH ADH GnRH Oxytocin Cytoplasm Figure 16.3

  20. Amino Acid-Based Hormone Action: PIP Mechanism Extracellular fluid Hormone 1 Receptor Gq Catecholamines TRH ADH GnRH Oxytocin Cytoplasm Figure 16.3

  21. Amino Acid-Based Hormone Action: PIP Mechanism Extracellular fluid Hormone 1 2 GTP Receptor Gq GDP GTP Catecholamines TRH ADH GnRH Oxytocin Cytoplasm Figure 16.3

  22. Amino Acid-Based Hormone Action: PIP Mechanism Extracellular fluid Hormone 1 2 3 PIP2 GTP GTP Receptor Gq GDP GTP Phospholipase C Catecholamines TRH ADH GnRH Oxytocin Cytoplasm Figure 16.3

  23. Amino Acid-Based Hormone Action: PIP Mechanism Extracellular fluid Hormone DAG 1 4 2 3 PIP2 GTP GTP Receptor Gq GDP GTP IP3 Phospholipase C Catecholamines TRH ADH GnRH Oxytocin Cytoplasm Figure 16.3

  24. Amino Acid-Based Hormone Action: PIP Mechanism Extracellular fluid Hormone DAG 1 4 5 Active protein kinase C 2 3 PIP2 GTP GTP Receptor Gq Inactive protein kinase C GDP GTP IP3 Phospholipase C Catecholamines TRH ADH GnRH Oxytocin 5 Endoplasmic reticulum Cytoplasm Ca2+ Figure 16.3

  25. Amino Acid-Based Hormone Action: PIP Mechanism Extracellular fluid Hormone DAG 1 4 5 Active protein kinase C 2 3 PIP2 GTP GTP Receptor Gq Inactive protein kinase C GDP GTP IP3 Phospholipase C Catecholamines TRH ADH GnRH Oxytocin Triggers responses of target cell 5 Endoplasmic reticulum 6 Cytoplasm Ca2+ Ca2+- calmodulin Figure 16.3

  26. Steroid Hormones • This interaction prompts DNA transcription to produce mRNA • The mRNA is translated into proteins, which bring about a cellular effect

  27. Structure of Intracellular Receptors These receptors are composed of a single polypeptide chain that has three distinct domains: • The amino-terminus: Involved in activating or stimulating transcription by interacting with other components of the transcriptional machinery. The sequence is highly variable among different receptors.

  28. DNA binding domain: Amino acids in this region are responsible for binding of the receptor to specific sequences of DNA. • The carboxy-terminus or ligand-binding domain: This is the region that binds hormone.

  29. In addition to these three core domains, two other important regions of the receptor protein are: • A nuclear localization sequence, which targets the the protein to nucleus, and • A dimerization domain, which is responsible for latching two receptors together in a form capable of binding DNA.

  30. When hormone binds to receptor, a characteristic series of events occurs: • Receptor activation is that the receptor becomes competent to bind DNA. • Activated receptors bind to "hormone response elements", • Receptor binding stimulates transcription. • The hormone-receptor complex thus functions as a transcription factor.

  31. Steroid Hormones • This interaction prompts DNA transcription to produce mRNA • The mRNA is translated into proteins, which bring about a cellular effect

  32. Steroid hormone Cytoplasm Steroid hormone Receptor- chaperonin complex Receptor-hormone complex Molecular chaperones Hormone response elements Binding Chromatin Transcription mRNA mRNA Nucleus Ribosome New protein Translation Figure 16.4

  33. Steroid hormone Cytoplasm Figure 16.4

  34. Steroid hormone Cytoplasm Steroid hormone Figure 16.4

  35. Steroid hormone Cytoplasm Steroid hormone Receptor- chaperonin complex Figure 16.4

  36. Steroid hormone Cytoplasm Steroid hormone Receptor- chaperonin complex Receptor-hormone complex Molecular chaperones Figure 16.4

  37. Steroid hormone Cytoplasm Steroid hormone Receptor- chaperonin complex Receptor-hormone complex Molecular chaperones Hormone response elements Binding Chromatin Figure 16.4

  38. Hormone response elements Binding Chromatin Transcription mRNA Nucleus Figure 16.4

  39. Hormone response elements Binding Chromatin Transcription mRNA mRNA Nucleus Ribosome Figure 16.4

  40. Hormone response elements Binding Chromatin Transcription mRNA mRNA Nucleus Ribosome New protein Translation Figure 16.4

  41. Steroid hormone Cytoplasm Steroid hormone Receptor- chaperonin complex Receptor-hormone complex Molecular chaperones Hormone response elements Binding Chromatin Transcription mRNA mRNA Nucleus Ribosome New protein Translation Figure 16.4

  42. Target Cell Specificity • Hormones circulate to all tissues but only activate cells referred to as target cells • Target cells must have specific receptors to which the hormone binds • These receptors may be intracellular or located on the plasma membrane

  43. Target Cell Specificity • Examples of hormone activity • ACTH receptors are only found on certain cells of the adrenal cortex • Thyroxin receptors are found on nearly all cells of the body

  44. Target Cell Activation • Target cell activation depends on three factors • Blood levels of the hormone • Relative number of receptors on the target cell • The affinity of those receptors for the hormone • Up-regulation – target cells form more receptors in response to the hormone • Down-regulation – target cells lose receptors in response to the hormone

  45. Hormone Concentrations in the Blood • Hormones circulate in the blood in two forms – free or bound • Steroids and thyroid hormone are attached to plasma proteins • All others are not bound

  46. Hormone Concentrations in the Blood • Concentrations of circulating hormone reflect: • Rate of release • Speed of inactivation and removal from the body • Hormones are removed from the blood by: • Degrading enzymes • The kidneys • Liver enzyme systems

  47. Interaction of Hormones at Target Cells • Three types of hormone interaction • Permissiveness – one hormone cannot exert its effects without another hormone being present • Synergism – more than one hormone produces the same effects on a target cell • Antagonism – one or more hormones opposes the action of another hormone

  48. Control of Hormone Release • Blood levels of hormones: • Are controlled by negative feedback systems • Vary only within a narrow desirable range • Hormones are synthesized and released in response to: • Humoral stimuli • Neural stimuli • Hormonal stimuli

  49. Humoral Stimuli • Humoral stimuli – secretion of hormones in direct response to changing blood levels of ions and nutrients • Example: concentration of calcium ions in the blood • Declining blood Ca2+ concentration stimulates the parathyroid glands to secrete PTH (parathyroid hormone) • PTH causes Ca2+ concentrations to rise and the stimulus is removed

More Related