Intro Molecular Endocrinology

Question 1

5 mechanisms for intercellular communication

Answer 1

1. endocrine
2. autocrine
3. paracine
4. neural
5. contact-dependent

Question 2

Endocrine Signaling

Answer 2

travels to the blood to far away organ/tissue

Question 3

Autocrine Signaling

Answer 3

hormone does not travel in the blood and can act on itself or the same cell type

Question 4

Paracrine Signaling

Answer 4

hormone does not travel in the blood and only goes short distances to act on different cell type

Question 5

Contact-dependent signaling

Answer 5

the hormone is membrane bound and therefore the target cell and the signaling cell must make direct contact

Question 6

3 structural classes of hormones

Answer 6

1. peptide (including glycoprotein)
2. steroid (all derived from cholesterol except retnoic acid)
3. amines (tyrosine derived)

Question 7

Describe peptide hormone synthesis

Answer 7

Peptides have at the amino terminal a signal sequence that signals for the ribosome to move to the ER. The first peptide made is the pre-prohormone (not active) and this is what contains the signal sequence. Once at the ER, the peptide is synthesized into the lumen of the ER where the signal sequence gets cleaved by a peptidase leaving a pro hormone (still not active). Each prohormone has a specific peptidase that cleaves the pro domain off leaving an active hormone. Hormone is packaged into vesicles (golgi does the packaging) and is stored there until the cell receives a signal causing the vesicles to fuse with the plasma membrane causing them to fuse with plasma membrane via exocytosis.

Question 8

Where are the steroid hormones derived from? Include exceptions.

Answer 8

Cholesterol except for retnoic acid. Also, amine hormones T3 and T4 behave as steroids therefore are also considered steroid hormones.

Question 9

Describe steroid synthesis

Answer 9

start with cholesterol (C27) reacts with P450scc to make pregnenalone (C21) whose A ring is oxygenated by 3BHSD to progesterone (C21). From progesterone we can get the androgens, mineralocorticoids, and glucocorticoids by reacting with P450c17 (reaction is varied by regulating the activity of the enzyme via phosphorylation of the P450c17. Can also regulate by varying what enzymes are available in different tissues)

Question 10

What are the androgens?

Answer 10

dihydotestosterone (C19), testosterone (C19), estrogens (C18).

Question 11

What is the rate limiting step of steroid synthesis?

Answer 11

Formation of pregnenalone (C21) and getting the cholesterol into the inner mt membrane??

Question 12

What is an example of mineralocorticoids?

Answer 12

aldosterone (C21)

Question 13

What is an example of glucocorticoid?

Answer 13

cortisol (C21)

Question 14

Characteristics of steroids (nuclear receptors)?

Answer 14

uses a carrier protein, long half life, receptor is intracellular, mediated by receptor-hormone, is lipid soluble

Question 15

Characteristics of peptides (catecholamines)?

Answer 15

no carrier protein (unless IGF), water soluble, receptor on the cell membrane, short half life (minutes), mediated by 2nd messengers

Question 16

Describe the basics of G protein signaling

Answer 16

hormone binds to receptor and causes a conformational change that allows the alpha subunit to bind to GTP instead of GDP. Upon binding GTP, alpha dissociates from beta/gamma and activates another protein that leads to amplification of the signal via 2nd messengers.

Question 17

Describe cAMP 2nd messenger system

Answer 17

hormone binds to receptor, alpha subunit activated and travels to adenyl cyclase activating it and stimulating it to produce lots of cAMP (amplification). cAMP activates PKA which also phosphorylates many different enzymes (amp). Different hormones can bind to the same receptor and elicit the same response, ex glucagon and epinephrine in the liver (augmentation). PKA stimulates glycogenolysis by inhibiting glycogen synthase, stimulating phosphorylase kinase.

Question 18

Describe IP3/DAG/Ca2+ 2nd messenger system

Answer 18

hormone binds receptor, conformational change, alpha subunit of G protein activated, activates phospholipase C which cleaves PIP2 into IP3 and DAG. IP3 binds to receptors on the ER causing a release of Ca2+ into the cytosol. IP3 also activates CAM kinase which phosphorylates many enzymes. Ca2+ and DAG activate Protein kinase C which phosphorylates and activates many enzymes. Augmented because different hormones can bind to the same receptor and elicit the same cellular response.

Question 19

What is gating?

Answer 19

ion channels changing between open and closed conformations

Question 20

What are the different types of Ca++ channels in the ER/SR?

Answer 20

ion gated, ligand gated via IP3 and ryanodine.

Question 21

What ions move outward when the membrane potential is 0?

Answer 21

K, the only one with a high concentration inside the cell verses outside!!!

Question 22

What ions move inward when the membrane potential is 0?

Answer 22

Cl, Na, Ca.

Question 23

When do ions stop moving?

Answer 23

when the membrane potential is equal and opposite to the ion potential (Eion, aka chemical gradient)

Question 24

What is the reversal potential?

Answer 24

aka Eion. Determines which way the ions move and predicts the membrane potential based on ion movement

Question 25

2 mechanisms for Ca++ diffusion into cytosol?

Answer 25

Ca++ channels in the ER/SR and Ca++ permeant channels in the plasma membrane.

Question 26

2 examples of Ca++ channels in the ER/SR

Answer 26

1. IP3 gated channels on the ER | 2. ryanodine channels on the SR in skeletal and cardiac muscle

Question 27

5 examples of Ca permeant channels (ion channels!) in the plasma membrane

Answer 27

1. voltage-gated Ca channels (CaV) 2. transient receptor potential channels (TRP) 3. Store operated Ca channels (Oria, SOCe) 4. mach receptor (neurotransmitter-gated) 5. glutamate NMDA receptor (neurotransmitter-gated)

Question 28

How does K regulate cytosolic Ca++ levels?

Answer 28

INDIRECTLY. If K+ channels open- membrane is hyperpolarized and the CaV channels can't open so less Ca in cytosol If K+ channels closed- membrane potential is depolarized and CaV channels are more open, so more Ca in cytosol

Question 29

Potassium Aggravated Myotonias (PAM)

Answer 29

defect in the NaV channels resulting in more Na in the skeletal muscle cells than normal, so they are hyper-excitable. Results in myotonia (prolonged contraction) then eventually paralysis. Comes in the form of attacks precipitated by exercising, foods rich in K, or stress. Not a very common disease. - gain of function - persistant NaV current because the NaV channels aren't able to inactivate as quickly - more positive RMP so easier to activate NaV channels

Question 30

What would happen if K+ outside the cell were higher than normal?

Answer 30

Cin/Cout would be smaller, resulting in a less negative membrane potential. Depolarized.

Question 31

What would happen if a small amount of NaV channels were always open?

Answer 31

Cin/Cout would get bigger, so the membrane potential would be more positive and depolarized.

Question 32

What would happen to membrane potential if most NaV channels were inactivated?

Answer 32

no Na would be able to enter the cell, so no AP.