(22) Regulation/Mechanisms of Action Flashcards
(Signal Pathways)
Most physiology pathways incorporate variations of these pathways which are highly conserved in animals ranging from worms to humans
signal molecule (first messenger) –> (1) binds to what? —> (2) which activates what? —> (3) which alters what? —-> which creates what (4)?
- How do hormones achieve specificity?
(1) receptor protein
(2) intracellular signal molecules (calcium)
(3) target proteins
(4) cellular response
5. receptors

(regulation of hormone secretion receptors and target cells)
- Receptors are couped to what that produce the physiological response?
- Is the magnitude of response correlated with hormone concentration? As the hormone concentration increases, what occurs?
(sensitivty)
let’s say there is a hormone concentration that produces 50% of maximal response - if more hormone is required to produce the 50%, has there been an increase or decrease in the sensitivy of the target tissue?
- cellular mechanisms
- yes; response increases and levels off
- decrease
(Regulation of hormone receptors)
1-2. Target tissue responsiveness (or sensitivity) to a hormone can be changed by what two things?
- changing affinity of the receptors for the hormone
- changing the number of receptors
(regulation of hormone receptors)
- What is it called when the number of receptors or the affinity of the receptors for the hormone has decreased?
2-4. what are three ways to achieve this?
- How would you up regulate?
- down-regulation
- decreasing synthesis of new receptors
- increasing degradation of existing (protesomes and enzymes do this)
- inactivating receptors
- do the opposite!!
(Regulation of hormone receptors)
- the greater the number of receptors for a hormone, the greater the maximal resopnse?
- The higher the affinity of the receptor for the hormone, the greater the likelihood of the response?
- What is the purpose of down regulation?
- As down reg occurs, the response to horome declines, although what?
- yes
- yes
- reduce sensitivty of target tissue when hormon levels are high
- hormone levels remain high
(examples of regulation)
(down regulation)
- what decreases the sensitivy of TRH receptors in the Anterior Pituitary?
- What reduce the responsiveness of the HT-AP-thyroid axis?
(up regulation)
- what up-regulates uterine receptors and also up-regulates LH receptors in the ovaries
- What up regulates prolactin receptor number in breast tissue?
- T3
- high levels of T3
- estrogen
- prolactin
(How do hormones change their target cells?)
Two fundamental mechanisms
what are they?
- activation of enzymes and othe molecules via 2nd messengers
- modulation of gene expression via gene transcription
(Receptor Protein)
- What three places are receptors in cell?
- What type can diffuse through the bilayer to access cytosolic or nuclear receptors? receptor activation turns on what? how fast?
- What type remain in extracellular fluid and bind to receptor proteins on the cell membrane? how fast is response? due to what?
- What does signal transduction do?
- nucleus, cytosol, cell membrane (where a chemical signal binds to its receptor depends on whether the signal molecule can enter the cell)
- lipophilic; turns on gene activation and directs the nucleus to make new mRNA transcription; slow (hours)
- lipophobic; very rapid; signal transduction (process by which an extracellular signal molecule activates a membrane receptor that in turn alters intracellular molecules to create a response)
- converts one form of signal into a different form
(Hormone REceptors; two types)
- What classes of hormones typically hand with cell surface receptors?
- intracellular receptors?
- do steroids also have some activity at the membrane level? why?
- proteins, peptides, catecholamines, and eicosanoids
- steroid and thyroid hormones
- yes; when they need a fast response (mostly adrenal steroids do this)

(how do hormones change their target cells?)
- activation of enzymes and other molecules via 2nd messengers
- Most enzymes shuttle between conformational states that are what verus what?
- How do hormones take advangate of this? usually causing what?
- catalytically active vs. inactive (on vs off)
- inducing such transitions; activation of one or more enzyems
(How do hormones change their target cells?)
(Modulation of gene expression via gene transcription)
- Stimulating transcription of a group of genes can lead to what?
- if transciption of a group of previosly active genes is shut off what will occur?
- burst of synthesis of new proteins
- corresponding proteins will disappear from the cell
(Hormone Receptors, Type 1: cell surface receptors sturcutre)
- What are the several variations? (3 of them)
- are molecules isolated by themselves or fixed in one location of the membrane? May other membrane proteins interact with the receptors?
- What is the key to generating the 2nd messengers and getting the hormone signal?
- simple, multisubunit, and complex
- no; yes
- interaction of h-r product with other proteins
(Hormone receptor type 1: 2nd messenger systems)
- Type 1 mechanisms of hormone action on target cells. There are second messengers - what are they?
- Do different hormones utlilze combinations of these systems?
- In all cases, the seemingly small singal generated by hormone binding its receptor is amplified within the cell into a cascade of actions that changes the cell’s physiologic state
- adenylyl cyclase (cyclic AMP), phospholipase C (calcium and/or phosphoinositides), tyrosine kinase, guanylate cyclase (c GMP)
- yes
(Hormone receptors, type 1: cell surface receptors)
just read this slide

and this one

second messenger system

activateing the g protein

look at this slide too - sorry - just easier this way

(Then what?)
- levels of cAMP decrease due to what?
- Hormone action was to modify the activity of what?
- Examples of other hormones which utlilize this system: E, NE, LH, FSH, TSH, calcitonin, PTH, ADH
- breakdown by cAMP-phophodiesterase and the inactivation of adenylate cyclase
- pre-existing cell components
(Fate of the Hormone Receptor Complex)
- Normal cell function depends upon second messenger cascades being what?
- What are associated with reecptors that continually stimulate second messenger systems?
- What is one important part of negative regulation of hormone action? Internalization is stimulated by what?
- internaliziton occurs by what? The resulting endosomes (receptosomes) may fuse with what? which leads to what? What can occur in other cases
- transient events
- cancers
- cell surface receptors are internalized; hormone binding
- endocytosis; lysosomes; leading to destruction of the receptor and hormone; hormone dissociates and the receptor is recycled by fusion of the endosome back into the plasma membrane
just take a gander - don’t memorize!!! she says she will not ask us about this - just understand concepts

(Intracellular receptors)
- receptors located where?
- Funcation as what?
- H-R complex binds to promoter regions of genes and does what?
- what do they modulate?
- inside target cells (cytoplasm or nucleus)
- ligan-dependent transcription factors
- (+) or (-) on gene transcription
- gene expression in target cells
(Intracellular receptor binding and DNA reactions)
- how do steroids (lipids) enter?
- How to thyroids enter?
- simple diffusion
- faciliated diffusion
- What is the most common method of cell communication?
- exogenous moleculs is received by a cell, and converted (transduced) into a what?
- is the pattern similar in all cells? did it evolve early - even before first multi-cellular cells?
- is it highly conserved in today’s ancestral cells?
- signal transduction
- response by the receiving cell
- yes; yes
- yes

(Cystolic or nuclear receptors)
- What two ends do they have?
- amino terminus and carboxy terminus (hormone-binding domain)

(Intracellular receptor binding and DNA reactions)
Hormone meets receptor and initiates series of events
- Receptor activation: conformational changes in what? becomnes competent to bind what?
- Activated receptors bind to what?
- What occurs then?
+ look at slide
- receptor; bind DNA
- to hormone response element (DNA seq)
- transcription from genes occurs

(intracelular binding)
- Are new proteins created specific to the hormone? do they account for specificity of a hormones action?
- What induces Ca binding protein that promotes Ca absoprtion from the intestine?
- what induces Na channels in renal principal cells (promote Na reabsorption in the kidney)?
- What induces synthesis of skeletal muscle proteins?
- yes; yes
- calcitriol
- aldosterone
- testosterone