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Can someone explain these steps of the Endocrine System?

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1. Hormone A (first messenger) binds to its receptor, which then binds to a G protein (G s)

2. G protein is then activated as it binds to GTP, displacing GDP

3. Activated G protein activates (stimulates) the effector enzyme adenylate cyclase

4. Adenylate cyclase generates cAMP (second messenger) from ATP

5. cAMP activates protein kinases, which then cause callular effects

i am so lost :crying2:

1. Hormone A (first messenger) binds to its receptor, which then binds to a G protein (G s)

2. G protein is then activated as it binds to GTP, displacing GDP

3. Activated G protein activates (stimulates) the effector enzyme adenylate cyclase

4. Adenylate cyclase generates cAMP (second messenger) from ATP

5. cAMP activates protein kinases, which then cause callular effects

i am so lost :crying2:

I wish I could draw a picture on here, it would help a lot, but I'll try with words. I'll try to keep it simple, but if I lapse into biochemistry babble forgive me, that's my background and I think things often make more sense when more information is provided.

First and foremost understand that the function of this whole mechanism is to transduce extracellular signals, like a hormone, into intracellular changes. Keep that in mind throughout this explanation, why is this a good system? Why does this work? Also, compare this process to the action of steroid hormones if you've gotten there yet.

What is happening here is that the hormone is binding to a specific receptor on the membrane of a target cell. These receptors, known as G-protein coupled receptors (GPCR), have 3 main components: Extracellular (which binds the hormone), transmembrane, and intracellular (which interacts with the G-protein). When the extracellular part binds the hormone, there is activation (by conformational change) of the intracellular part which interacts with the G-protein.

The G-protein in its resting state is bound to GDP. When the GPCR is activated the G-protein is activated to swap GDP for GTP which activates it. Actually what's happening is that the G-protein is originally in 3 components (alpha, beta, and gamma), and the binding of GTP allows the dissociation of the alpha unit from the beta-gamma unit. When freed from the beta-gamma unit, the alpha unit is free to activate adenylate cyclase until it hydrolyzes GTP to GDP, and rejoins the beta-gamma unit in the inactive conformation.

The main action of adenylate cyclase is to synthesize cAMP from ATP. cAMP in turn activates protein kinases which are enzymes which add phosphates to proteins. Phosphorylation and dephosphorylation are very common methods of modifying the activity of different enzymes in the cell - this is a very smart system, because if you can turn already made proteins on or off, especially in conjunction with each other, you don't have to waste energy making and degrading proteins constantly. So, for example, cellular effects of say glucagon stimulation (which acts through a GPCR) would include turning off enzymes that store glucose as glycogen and/or shut off glucose breakdown, in both cases to allow glucose to be returned to the blood to raise blood glucose. Once glucose levels are high again, other enzymes can come in and dephosphorylate the enzymes that glucagon shut off to allow the opposite process to work.

Does this help at all? Please feel free to ask any questions, I can go way more in depth or perhaps less in depth if you want. GPCRs are really important from a clinical perspective since they are the most important class of drug targets (60% or so of pharmaceutical drugs work on GPCRs).

thank you.

this is what i have come up with:

1) hormone (1st messenger) binds to its receptor

2) receptor changes share and binds to nearby inactive G protein

3) in the activated state, GDP is bound to G protein

4) G protein releases GDP and GTP binds to G protein instead

5) part of G protein with GTP attached travels to Adenylate cyclase and activates it

6) Adenylate cyclase initiates conversion of ATP to cAMP (cAMP is 2nd messenger)

7) cAMP activates protein kinases A

is that right?

im also kinda confused about this too.

my teacher wrote:

TRH---> TSH---> thyroid---> T3, T4, and calcitonin

does this mean..

the hypothalamus releases TRH which tells the anterior pituitary to release TSH. TSH travels to the thyroid which makes the thyroid release T3, T4, or calcitonin

im confused as to what releases what, etc

You've almost got it, I just want to clarify this:

3) in the activated state, GDP is bound to G protein - It would be more correct to say that in the inactive state GDP is bound to G protein. Technically when the receptor is first activated you are correct but this change happens very fast so it's better just to think of it as GDP-inactive, GTP-active

As for the TSH pathway it's looking right to me, TRH, Thyrotropin releasing hormone, comes from the hypothalamus and triggers the release of TSH, thyroid stimulating hormone, from the anterior pituitary. TSH in turn acts on the thyroid to cause secretion of T3 and T4. It might be worth noting that the hypothalamus can also release somatostatin, which has the opposite effect on TSH.

As well, this pathway is a good example of 2 things I guarantee you'll see again:

1.) Negative feedback - As it sounds, end product inhibition of something farther up in the pathway to stop it's own release and/or production. Here, if T3 and T4 are high, TSH production is suppressed.

2.) Hypophysiotropic hormones in TRH - all hormones of this type act as part of a 3-part deal, release of hormone A (TRH) from hypothalamus to stimulate release of hormone 2 (TSH) in anterior pituitary to stimulate action in an endocrine gland (here, the thyroid). Other hormones of this type include GnRH (sex hormones), GHRH (growth hormone), CRH (ACTH), etc.

You've almost got it, I just want to clarify this:

3) in the activated state, GDP is bound to G protein - It would be more correct to say that in the inactive state GDP is bound to G protein. Technically when the receptor is first activated you are correct but this change happens very fast so it's better just to think of it as GDP-inactive, GTP-active

As for the TSH pathway it's looking right to me, TRH, Thyrotropin releasing hormone, comes from the hypothalamus and triggers the release of TSH, thyroid stimulating hormone, from the anterior pituitary. TSH in turn acts on the thyroid to cause secretion of T3 and T4. It might be worth noting that the hypothalamus can also release somatostatin, which has the opposite effect on TSH.

As well, this pathway is a good example of 2 things I guarantee you'll see again:

1.) Negative feedback - As it sounds, end product inhibition of something farther up in the pathway to stop it's own release and/or production. Here, if T3 and T4 are high, TSH production is suppressed.

2.) Hypophysiotropic hormones in TRH - all hormones of this type act as part of a 3-part deal, release of hormone A (TRH) from hypothalamus to stimulate release of hormone 2 (TSH) in anterior pituitary to stimulate action in an endocrine gland (here, the thyroid). Other hormones of this type include GnRH (sex hormones), GHRH (growth hormone), CRH (ACTH), etc.

thanks!! i fixed it :)

hypocaffeinemia, BSN, RN

Specializes in Critical Care.

my teacher wrote:

TRH---> TSH---> thyroid---> T3, T4, and calcitonin

does this mean..

the hypothalamus releases TRH which tells the anterior pituitary to release TSH. TSH travels to the thyroid which makes the thyroid release T3, T4, or calcitonin

im confused as to what releases what, etc

That's basically it. Here's a good chart: http://www.ehponline.org/members/1998/Suppl-6/1263-1270carpenter/carpenterfig3B.GIF

Two small details, however:

  1. The thyroid only produces a minimum amount of T3. Most T3 is formed at the cellular level by the deiodinization of T4.
  2. T3 and to a lesser extent T4 work in a negative feedback loop to inhibit the production of TSH. This is why high TSH levels are seen in hypothyroidism and conversely, low TSH levels in hyperthyroidism.

How can I get 'permission' to view this website? It states permission is needed.

Thanks!

This was a fabulous beginning to her question, which is the beginning of a beautiful thing to MY question...so, if you have time to elaborate, take it from where you left off and relate it to hyperthyroidism at the cellular level?....thanks in advance!

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