Steroid hormone and nuclear receptors

[ChessMaster3000]

I read sometimes that steroid hormones (as in glucocorticoids) have cytoplasmic receptors and sometimes have nuclear receptors. ON another thread in this forum from a long time ago, someone wrote that steroid hormones don't need cytoplasmic receptors--what does that mean? How do you know when/if a steroid hormone needs a cytoplasmic receptors and when it doesn't? I do understand that thyroid hormone, Vitamin A, and Vitamin D rely on nuclear receptors.

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[MudPhud20XX]

As far as our board is involved, I would say lipid soluble hormone (steroids + thyroid hormone) have receptors in the nucleus.
Basically no receptors for steroid hormone.
Kaplan physiology from general aspects of the endocrine system has a nice summary/comparison between lipid vs water soluble hormones.

Has anyone seen any q bank question trying trick you with this concept?

 

[ChessMaster3000]

As far as our board is involved, I would say lipid soluble hormone (steroids + thyroid hormone) have receptors in the nucleus.
Basically no receptors for steroid hormone.
Kaplan physiology from general aspects of the endocrine system has a nice summary/comparison between lipid vs water soluble hormones.

Has anyone seen any q bank question trying trick you with this concept?

I'm sorry--when you say "basically no receptors for steroid hormone" what does that mean??

Per wiki: glucocorticoid receptors in the cytosol:
http://en.wikipedia.org/wiki/Glucocorticoid_receptor

 

[ChessMaster3000]

And thanks for your help!

 

[MudPhud20XX]

Sorry I meant to say no cell/cytoplasmic receptors for steroid hormone.

 

[ChessMaster3000]

Sorry I meant to say no cell/cytoplasmic receptors for steroid hormone.

Ok, is that according to Kaplan? Do you have any idea why wikipedia would say the opposite? I could understand there being both cytoplasmic and nuclear receptors, but it seems weird that some sources say nuclear and some say cytosolic exclusviely

 

[Donald Juan]

According to what I just watched on Kisspharm, all pertinent hydrophobic hormones have nuclear receptors except for cortisol which has a cytoplasmic receptor. Even still, cortisol binds to its receptor and then the cortisol-CR complex can either enter the nucleus or have affects in the cytoplasm.

Thyroid hormone is the exception in the other way. It is typically charged at physiologic pH, but it doesn't rely on a 2nd messenger system. Apparently there are transporters that allow the hormone to enter the cell so it can bind to its receptor in the nucleus.

 

[ChessMaster3000]

According to what I just watched on Kisspharm, all pertinent hydrophobic hormones have nuclear receptors except for cortisol which has a cytoplasmic receptor. Even still, cortisol binds to its receptor and then the cortisol-CR complex can either enter the nucleus or have affects in the cytoplasm.

Thyroid hormone is the exception in the other way. It is typically charged at physiologic pH, but it doesn't rely on a 2nd messenger system. Apparently there are transporters that allow the hormone to enter the cell so it can bind to its receptor in the nucleus.

I'm pretty sure testosterone and estrogen have receptors in the cytosol--are you arguing that is not the case? I have always learned they diffuse into the cytoplasm and bind receptors, release heat shock proteins, etc.

 

[notbobtrustme]

I'm pretty sure testosterone and estrogen have receptors in the cytosol--are you arguing that is not the case? I have always learned they diffuse into the cytoplasm and bind receptors, release heat shock proteins, etc.

yea, that's how I learned it. When steroids bind receptors in the cytoplasm, they become transcription factors in the nucleus (or activate TF in the nucleus) and imitate gene transcription.

 

[alicealicealice]

In my notes, I have
Vitamin A, Vitamin D, T3/T4 enter the cell by faciltiated diffusion and bind to receptors int he nucleus, which then bind to DNA upstream of the target geen using Zn finger motif.
Test,progesterone, cortisol, and aldo enter the cell by simple diffusion, bind to cytoplasmic receptor, and go to the nucleus, and bind upstream of target gene using Zn finger motif.
This file, compiled by other users, was posted here sometime in the past.
That file combined with the mneumonics in FA for secondary receptors (qiss qiq siq sqs, FLAT ChAMP, PIG, etc) work well together for anything you come across in questions

 

[Donald Juan]

I'm pretty sure testosterone and estrogen have receptors in the cytosol--are you arguing that is not the case? I have always learned they diffuse into the cytoplasm and bind receptors, release heat shock proteins, etc.

You're right, maybe the point the guy was making is that cortisol has specific affects in the cytoplasm, which still doesn't seem to be 100% accurate.

 

[ChessMaster3000]

You're right, maybe the point the guy was making is that cortisol has specific affects in the cytoplasm, which still doesn't seem to be 100% accurate.

great pdf doc. I think it is safe to keep it simple and go with cortisol receptors in the cytoplasm. Btw, Kisspharm is great, but there are a number of things on there that aren't 100% accurte, so just beware.

 

[ChessMaster3000]

In my notes, I have
Vitamin A, Vitamin D, T3/T4 enter the cell by faciltiated diffusion and bind to receptors int he nucleus, which then bind to DNA upstream of the target geen using Zn finger motif.
Test,progesterone, cortisol, and aldo enter the cell by simple diffusion, bind to cytoplasmic receptor, and go to the nucleus, and bind upstream of target gene using Zn finger motif.
This file, compiled by other users, was posted here sometime in the past.
That file combined with the mneumonics in FA for secondary receptors (qiss qiq siq sqs, FLAT ChAMP, PIG, etc) work well together for anything you come across in questions

On the topic, what is the place of receptor serine/threonine kinase in all of this? I know that MAPK is serine/threonine specific, but the only information about these receptors I have found is that they are the signal mech for TGF-B. Are there other ligands for which this "phrase", if you will, is relevant as pertains to the exam?

 

[Transposony]

There are five major categories of steroid hormone receptors: estrogen receptors (ER), androgen receptors (AR), progestin receptors (PR), glucocorticoid receptors (GR), and mineralocorticoid receptors (MR). Each group contains membrane, cytoplasmic, or nuclear receptors based on the receptor proteins location in the cell - outside in the plasma membrane, or inside in the cytoplasm or the nucleus.
The most well studied steroid hormone receptors are those located inside the cell. Because the molecular structure and function of these receptors are the same whether they are in the cytoplasm or nucleus, these receptors are usually lumped together as nuclear receptors.


This is what Kaplan says:
Steroid Hormone Receptors (SHR) act as hormone dependent nuclear transcription factors. Upon entering the cell by passive diffusion, the hormone (H) binds the receptor, which is subsequently released from heat shock proteins, and translocates to the nucleus. There, the receptor dimerizes, binds specific sequences in the DNA, called Hormone Responsive Elements or HREs, and recruits a number of coregulators that facilitate gene transcription.

 

[Transposony]

On the topic, what is the place of receptor serine/threonine kinase in all of this? I know that MAPK is serine/threonine specific, but the only information about these receptors I have found is that they are the signal mech for TGF-B. Are there other ligands for which this "phrase", if you will, is relevant as pertains to the exam?

There are various Protein Kinases and they are mainly divided into Receptor Protein Kinases & Cytosolic Protein Kinases.
So there are:
1. Receptor Tyrosine Kinases & Cytosolic Tyrosine Kinases

2. Receptor serine/threonine Kinases & Cytosolic serine/threonine Kinases

3. Receptor Tyrosine/threonine Kinases & Cytosolic Tyrosine/threonine Kinases

RAF, and MAPK are both serine/threonine-selective Cytosolic protein kinases.

Whereas Receptor serine/threonine Kinases acts as signal mechanism for TGF-B inflammtory/apoptotic pathway.

 

[Miracoli]

There is a lot of confusion. I will try to make it clear.
Receptors can be i) surface membrane receptors ii) nuclear receptors
NUCLEAR RECEPTORS
- includes those receptors for the glucocorticoids, mineralocorticoids, androgens, progesterone, estrogens, thyroid hormone, and vitamin D
- even though some receptors are compartmentalized in the cytoplasm (eg, glucocorticoid receptor), whereas others are confined to the nucleus (eg, thyroid hormone receptor), all of them are called NUCLEAR receptors because they all operate within the nuclear chromatin to initiate the signaling cascade.
-they are divided into
a) STEROID RECEPTOR Family
-includes GR Glucocorticoid receptor, MR Mineralocorticoid receptor, AR androgen rceptors , and PR Progesterone receptor
-they are located in the cytoplasm in association with HSP (but they are called nuclear receptors)
-when the receptor binds to the ligand, it dissociates from HSP and recptor-ligand is translocated to nucleus to bind to the HRE in the DNA
a)THYROID RECEPTOR Family
-Includes the TR Thyroid hormone receptor, RAR RXR(Retinoic acid receptors), , ER Estrogen receptor, PPAR Peroxisome proliferator–activated receptor, and VDR Vitamin D receptor
-they are located in the nucleus: with the exception of the ER, they do not associate with the HSPs, and they are constitutively bound to chromatin in the cell nucleus
-The ER binds to its RE as a homodimer, whereas the VDR, RAR, RXR, and TR prefer binding as heterodimers, heterodimer formed for example by binding to RXR

 

[alicealicealice]

^ Miracoli we are in agreement about locations. It looks like Estrogen receptors can be found in both the cytosol and nucleus, so I don't think that distinction is testable. http://en.wikipedia.org/wiki/Estrogen_receptor

As transposony said, serine/threonine receptors are associated with TGF beta among others, but I haven't really come across any really emphasized pathways involving them for the test.

However, @ChessMaster3000 a recent U World q (that was completely new to me but wouldn't be surprised if you guys knew) said that the major mechanism for induction of insulin resistance by TNFa, corticosteroids, glucagon and cathecholamines is that they cause phosphorylation of the serines and threonines on the Insulin receptor and the insulin receptor substrates (which are normally activated by tyrosine phopshorylation; insulin receptor is a dimeric RTK). By phosphorylating the serine/threonine residues instead of the tyrosine residues, that effectively shut the pathway down even in the presence of insulin and prevent the translocation of GLUT4 to the membrane.

 

[ChessMaster3000]

^ Miracoli we are in agreement about locations. It looks like Estrogen receptors can be found in both the cytosol and nucleus, so I don't think that distinction is testable. http://en.wikipedia.org/wiki/Estrogen_receptor

As transposony said, serine/threonine receptors are associated with TGF beta among others, but I haven't really come across any really emphasized pathways involving them for the test.

However, @ChessMaster3000 a recent U World q (that was completely new to me but wouldn't be surprised if you guys knew) said that the major mechanism for induction of insulin resistance by TNFa, corticosteroids, glucagon and cathecholamines is that they cause phosphorylation of the serines and threonines on the Insulin receptor and the insulin receptor substrates (which are normally activated by tyrosine phopshorylation; insulin receptor is a dimeric RTK). By phosphorylating the serine/threonine residues instead of the tyrosine residues, that effectively shut the pathway down even in the presence of insulin and prevent the translocation of GLUT4 to the membrane.

Yes I learned that through UW as well--I havent seen it anywhere else, and I doubt it will be on the test, but nonetheless good to know. Also, I dont think the phosphorylation of serine/thr precludes the intrinsic receptor tyrosine kinase activity- so even if the tyrosine is phosphorylated like normal, the IRS can still be phosphorylated at serine/thr which would decrease sensitivity. All i'm saying is that its not mutually exclusive (tyrosine vs ser/thr phosphorylation). Couldn't matter less for the test.

 

[Miracoli]

^ Miracoli we are in agreement about locations. It looks like Estrogen receptors can be found in both the cytosol and nucleus, so I don't think that distinction is testable. http://en.wikipedia.org/wiki/Estrogen_receptor

As transposony said, serine/threonine receptors are associated with TGF beta among others, but I haven't really come across any really emphasized pathways involving them for the test.

However, @ChessMaster3000 a recent U World q (that was completely new to me but wouldn't be surprised if you guys knew) said that the major mechanism for induction of insulin resistance by TNFa, corticosteroids, glucagon and cathecholamines is that they cause phosphorylation of the serines and threonines on the Insulin receptor and the insulin receptor substrates (which are normally activated by tyrosine phopshorylation; insulin receptor is a dimeric RTK). By phosphorylating the serine/threonine residues instead of the tyrosine residues, that effectively shut the pathway down even in the presence of insulin and prevent the translocation of GLUT4 to the membrane.

@alicealicealice, i see that i joined the party very late
About the increased phosphrylation of serine/threonine, and decreased tyrosine phosphorylation, it is not new, i remember my endocrine prof was discussing it a while ago.
Check out this article from 199
Molecular mechanisms of insulin resistance.
Pillay TS, Makgoba MW - S. Afr. Med. J. - May 1991; 79(10); 607-13
Receptor-mediated insulin resistance may be a consequence of various factors including increased serine/threonine phosphorylation of the receptor with decreased tyrosine phosphorylation, receptor desensitization, auto-antibodies to the receptor and inherited structural defects in the insulin receptor. Defects in insulin action could also arise at post-receptor events particularly glucose transport. Other circulating hormones, such as the newly characterised islet amyloid polypeptide (amylin), may also cause insulin resistance.

serine phosphorylation of IRS proteins can reduce their ability to attract PI 3-kinase, thereby minimizing its activation and also results in increased degradation and downregulation of IRS. This is from 2006 article http://diabetes.diabetesjournals.org/content/55/8/2392.long