Lecture 14: Endocrine Principles of Hormone Action Flashcards
What are the multiple actions that hormones have?
-Hormones are secreted in the blood and act at a distance from the release site
-Need to level in blood (depends on solubility ie if have carrier proteins or free), survive long enough, and be active at the target site
-Hormones trigger specific actions in specific target cells, requirement for specific recognition: RECEPTORS = key that recognizes hormone with specific binding
-Principle of action is based on hormone biochemical structure and properties
What are the effects on receptors from the 2 different major classes of hormones? (water and lipo)
-Hormones binding to receptors initiate the effetcs
Lipophilic hormones
-Diffuse out of producing cells
-Circulate mainly bound to carriers in the blood
-Diffuse in target cells to intracellular receptors
Water-soluble hormones
-Packaged and secreted (exocytosis)
-Circulate free in blood
-Stay out of target cell leading to surface receptors (Extracellular) which imitates cascade of events
What are types of lipophilic hormones?
-Steroids
-Thyroid hormones
Explain the importance of a carrier protein in blood
Steroid and thyroid hormones
-Insolubale in water so circulate associated to carrier proteins
-Some carriers are specific= globulins (CBG, DBG, SHBG, TBG) and some non-specific (albumin and prealbumin)
-Carrier proteins are big: keep hormones in vessel, prevent hormone degradation
-Reversible (hormone + carrier -> <- hormone- carrier)
-A small portion remains free and diffuses to the tissues
-Free hormones is the active portion, but is also susceptible to degradation
-Free form (active) is involved in feedback loops
-Carrier: serves as “hormone reservoir” (once bound is protected but not active) “hormone buffer”(increase particular hormone help to keep in blood but not used) “hormone protection”
TRUE OR FALSE: Carrier proteins play a major role in controlling Lipophilic hormones.
TRUE
What is the difference between free and bound hormones in circulation? Explain the process of how they bind to target tissue/receptor.
-Free hormones diffuse through plasma membrane of target
-Binds to a specific intracellular receptor= nuclear hormone receptor (NHR)
-Hormone-receptor complex translocates to the nucleus and binds to septic DNA sequences (response element)
-Stimulates gene expression –> de novo protein synthesis
-NHR are considered “transcription factors”
-In case of thyroid hormones, NHR is already in the nucleus and hormones diffuse all the way there
What are the different parts of the nuclear hormone receptor?
-Ligand binding domain: binds hormone (ie recognized by hormone)
-DNA binding domain: binds DNA of target gene
-Activation domain: stimulates gene transcription (modulates transcription)
-Orphan receptor: NHR cloned but no ligand found (yet) (know structurally is hormone receptor but ligand binding domain not yet found yet)
What is the action of lipophilic hormones?
-The action affects the synthesis of new proteins by gene regulation = slow-acting hormones (go through all processes above)
Case of Thyroid hormones:
-Major circulating form is T4 (thyroxine)
-When it enters target cell –> converted to T3 (tai-iodine thyronine) the cellular active form
-Binds to its specific receptor after entering the nucleus
-After acting, hormones dissociate from the receptor, can be partly degraded in target cells (thyroid hormones), then goes back to circulation and is degraded in the liver
What are types of water-soluble hormones?
-Proteins
-Catecholamines
How do water-soluble hormones circulate and enter tissues?
-Cant pass the phospholipid membrane barrier
-Secreted in vesicles regulated by exocytosis, circulate free (exception: IGF-1 circulates bound to carrier)
-Bind to specific receptors on surface of target cell
-Do not enter the cell to act –> need second messengers
-Receptor is key mediator b/w hormone and second messengers
What are the different areas of the cell surface receptor?
-Hydrophobic region “hiding” in the membranes phospholipids (transmembrane domain: TMD)
-Hydrophilic regions located outside (extracellular domain: ECD) and inside (intracellular domain: ICD) the cell
-Hormone-receptor –> activation of intracellular second messengers
What are the different areas of the cell surface receptor?
-Hydrophobic region “hiding” in the membranes phospholipids (transmembrane domain: TMD)
-Hydrophilic regions located outside (extracellular domain: ECD) and inside (intracellular domain: ICD) the cell
-Hormone-receptor –> activation of intracellular second messengers
What are the major types of cell surface receptors and messengers?
Receptor (messenger)
- G-proteins coupled (Adenylate Cyclase; cAMP and phospholipase C; Ca2+)
-Tyrosine kinase (Auto-phosphorylation)
-Interleukin/cytokine family (JAK-STAT)
-Serine kinase (TGFbeta) family (SMADs)
What are the steps in the G- protein coupled receptors?
a) Hormone binds to a receptor coupled to G-proteins (alpha,beta,gamma) inactive 3 coupled
b) Change in receptor conformation = exchange of GDP with GTP on Alpha SU(subunit)
c) Galpha SU dissociates from beta gamma Sis and activates a membrane protein
d) Activated membrane protein stimulates a cascade of second messengers
e)The second messengers elicit the biological response in the cell
There are 3 major types of G-proteins differing by their _______.
-alpha subunit
-Each class will elicit a different response DEPENDING ON THE ALPHA SUBUNIT
