(22) Regulation/Mechanisms of Action

Question 1

(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)?

5. How do hormones achieve specificity?

Answer 1

(1) receptor protein
(2) intracellular signal molecules (calcium)
(3) target proteins
(4) cellular response
5. receptors

Question 2

(regulation of hormone secretion receptors and target cells)

1. Receptors are couped to what that produce the physiological response?
2. 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?

Answer 2

1. cellular mechanisms
2. yes; response increases and levels off
3. decrease

Question 3

(Regulation of hormone receptors)

1-2. Target tissue responsiveness (or sensitivity) to a hormone can be changed by what two things?

Answer 3

1. changing affinity of the receptors for the hormone
2. changing the number of receptors

Question 4

(regulation of hormone receptors)

1. 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?

5. How would you up regulate?

Answer 4

1. down-regulation
2. decreasing synthesis of new receptors
3. increasing degradation of existing (protesomes and enzymes do this)
4. inactivating receptors
5. do the opposite!!

Question 5

(Regulation of hormone receptors)

1. the greater the number of receptors for a hormone, the greater the maximal resopnse?
2. The higher the affinity of the receptor for the hormone, the greater the likelihood of the response?
3. What is the purpose of down regulation?
4. As down reg occurs, the response to horome declines, although what?

Answer 5

1. yes
2. yes
3. reduce sensitivty of target tissue when hormon levels are high
4. hormone levels remain high

Question 6

(examples of regulation)

(down regulation)

1. what decreases the sensitivy of TRH receptors in the Anterior Pituitary?
2. What reduce the responsiveness of the HT-AP-thyroid axis?

(up regulation)

3. what up-regulates uterine receptors and also up-regulates LH receptors in the ovaries
4. What up regulates prolactin receptor number in breast tissue?

Answer 6

1. T3
2. high levels of T3
3. estrogen
4. prolactin

Question 7

(How do hormones change their target cells?)

Two fundamental mechanisms

what are they?

Answer 7

1. activation of enzymes and othe molecules via 2nd messengers
2. modulation of gene expression via gene transcription

Question 8

(Receptor Protein)

1. What three places are receptors in cell?
2. What type can diffuse through the bilayer to access cytosolic or nuclear receptors? receptor activation turns on what? how fast?
3. What type remain in extracellular fluid and bind to receptor proteins on the cell membrane? how fast is response? due to what?
4. What does signal transduction do?

Answer 8

1. nucleus, cytosol, cell membrane (where a chemical signal binds to its receptor depends on whether the signal molecule can enter the cell)
2. lipophilic; turns on gene activation and directs the nucleus to make new mRNA transcription; slow (hours)
3. 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)
4. converts one form of signal into a different form

Question 9

(Hormone REceptors; two types)

1. What classes of hormones typically hand with cell surface receptors?
2. intracellular receptors?
3. do steroids also have some activity at the membrane level? why?

Answer 9

1. proteins, peptides, catecholamines, and eicosanoids
2. steroid and thyroid hormones
3. yes; when they need a fast response (mostly adrenal steroids do this)

Question 10

(how do hormones change their target cells?)

1. activation of enzymes and other molecules via 2nd messengers
2. Most enzymes shuttle between conformational states that are what verus what?
3. How do hormones take advangate of this? usually causing what?

Answer 10

2. catalytically active vs. inactive (on vs off)
3. inducing such transitions; activation of one or more enzyems

Question 11

(How do hormones change their target cells?)

(Modulation of gene expression via gene transcription)

1. Stimulating transcription of a group of genes can lead to what?
2. if transciption of a group of previosly active genes is shut off what will occur?

Answer 11

1. burst of synthesis of new proteins
2. corresponding proteins will disappear from the cell

Question 12

(Hormone Receptors, Type 1: cell surface receptors sturcutre)

1. What are the several variations? (3 of them)
2. are molecules isolated by themselves or fixed in one location of the membrane? May other membrane proteins interact with the receptors?
3. What is the key to generating the 2nd messengers and getting the hormone signal?

Answer 12

1. simple, multisubunit, and complex
2. no; yes
3. interaction of h-r product with other proteins

Question 13

(Hormone receptor type 1: 2nd messenger systems)

1. Type 1 mechanisms of hormone action on target cells. There are second messengers - what are they?
2. Do different hormones utlilze combinations of these systems?
3. 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

Answer 13

1. adenylyl cyclase (cyclic AMP), phospholipase C (calcium and/or phosphoinositides), tyrosine kinase, guanylate cyclase (c GMP)
2. yes

Question 14

(Hormone receptors, type 1: cell surface receptors)

just read this slide

Answer 14

and this one

Question 15

second messenger system

Answer 15

activateing the g protein

Question 16

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

Question 17

(Then what?)

1. levels of cAMP decrease due to what?
2. Hormone action was to modify the activity of what?
3. Examples of other hormones which utlilize this system: E, NE, LH, FSH, TSH, calcitonin, PTH, ADH

Answer 17

1. breakdown by cAMP-phophodiesterase and the inactivation of adenylate cyclase
2. pre-existing cell components

Question 18

(Fate of the Hormone Receptor Complex)

1. Normal cell function depends upon second messenger cascades being what?
2. What are associated with reecptors that continually stimulate second messenger systems?
3. What is one important part of negative regulation of hormone action? Internalization is stimulated by what?
4. internaliziton occurs by what? The resulting endosomes (receptosomes) may fuse with what? which leads to what? What can occur in other cases

Answer 18

1. transient events
2. cancers
3. cell surface receptors are internalized; hormone binding
4. 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

Question 19

just take a gander - don’t memorize!!! she says she will not ask us about this - just understand concepts

Question 20

(Intracellular receptors)

1. receptors located where?
2. Funcation as what?
3. H-R complex binds to promoter regions of genes and does what?
4. what do they modulate?

Answer 20

1. inside target cells (cytoplasm or nucleus)
2. ligan-dependent transcription factors
3. (+) or (-) on gene transcription
4. gene expression in target cells

Question 21

(Intracellular receptor binding and DNA reactions)

1. how do steroids (lipids) enter?
2. How to thyroids enter?

Answer 21

1. simple diffusion
2. faciliated diffusion

Question 22

1. What is the most common method of cell communication?
2. exogenous moleculs is received by a cell, and converted (transduced) into a what?
3. is the pattern similar in all cells? did it evolve early - even before first multi-cellular cells?
4. is it highly conserved in today’s ancestral cells?

Answer 22

1. signal transduction
2. response by the receiving cell
3. yes; yes
4. yes

Question 23

(Cystolic or nuclear receptors)

1. What two ends do they have?

Answer 23

1. amino terminus and carboxy terminus (hormone-binding domain)

Question 24

(Intracellular receptor binding and DNA reactions)

Hormone meets receptor and initiates series of events

1. Receptor activation: conformational changes in what? becomnes competent to bind what?
2. Activated receptors bind to what?
3. What occurs then?

+ look at slide

Answer 24

1. receptor; bind DNA
2. to hormone response element (DNA seq)
3. transcription from genes occurs

Question 25

(intracelular binding)

1. Are new proteins created specific to the hormone? do they account for specificity of a hormones action?
2. What induces Ca binding protein that promotes Ca absoprtion from the intestine?
3. what induces Na channels in renal principal cells (promote Na reabsorption in the kidney)?
4. What induces synthesis of skeletal muscle proteins?

Answer 25

1. yes; yes
2. calcitriol
3. aldosterone
4. testosterone