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Author Topic: SHBG Controls Androgens (Testosterone, etc.) Inside the Cell!  (Read 8583 times)

doin it

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SHBG Controls Androgens (Testosterone, etc.) Inside the Cell!
« on: January 10, 2018, 08:02:01 pm »

https://www.ncbi.nlm.nih.gov/m/pubmed/16143106/

Full text:
 http://www.cell.com/cell/fulltext/S0092-8674(05)00651-3?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867405006513%3Fshowall%3Dtrue

Androgens and estrogens are transported bound to the sex hormone binding globulin (SHBG). SHBG is believed to keep sex steroids inactive and to control the amount of free hormones that enter cells by passive diffusion. Contrary to the free hormone hypothesis, we demonstrate that megalin, an endocytic receptor in reproductive tissues, acts as a pathway for cellular uptake of biologically active androgens and estrogens bound to SHBG. In line with this function, lack of receptor 

In line with this function, lack of receptor expression in megalin knockout mice results in impaired descent of the testes into the scrotum in males and blockade of vagina opening in females. Both processes are critically dependent on sex-steroid signaling, and similar defects are seen in animals treated with androgen- or estrogen-receptor antagonists.

doin it

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Re: SHBG Controls Androgens (Testosterone, etc.) Inside the Cell!
« Reply #1 on: January 10, 2018, 08:06:49 pm »
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136390/
(
Sex Hormone Binding Globulin (SHBG) is the major serum carrier of sex hormones. However, growing evidence suggests that SHBG is internalised and plays a role in regulating intracellular hormone action. This study was to determine whether SHBG plays a role in testosterone uptake, metabolism, and action in the androgen sensitive LNCaP prostate cancer cell line.

« Last Edit: January 11, 2018, 05:04:12 am by PeakT »

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Re: SHBG Controls Androgens (Testosterone, etc.) Inside the Cell!
« Reply #1 on: January 10, 2018, 08:06:49 pm »


SHBetaG

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Re: SHBG Controls Androgens (Testosterone, etc.) Inside the Cell!
« Reply #2 on: January 11, 2018, 04:48:36 am »
Nice find!
« Last Edit: January 11, 2018, 05:04:21 am by PeakT »

PeakT

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Re: SHBG Controls Androgens (Testosterone, etc.) Inside the Cell!
« Reply #3 on: January 11, 2018, 05:09:24 am »
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136390/
(
Sex Hormone Binding Globulin (SHBG) is the major serum carrier of sex hormones. However, growing evidence suggests that SHBG is internalised and plays a role in regulating intracellular hormone action. This study was to determine whether SHBG plays a role in testosterone uptake, metabolism, and action in the androgen sensitive LNCaP prostate cancer cell line.

Oh my goodness, what a gem.  This explains a heck of a lot in my opinion.

The thesis of this article is that you need SHBG INSIDE your cells for protection and inhibition of androgens.  Check out this statement:

"Testosterone was rapidly taken up and effluxed as testosterone-glucuronide; however this effect was reduced by the presence of SHBG. Addition of SHBG, rather than reducing testosterone bioavailability, further increased testosterone-induced expression of prostate specific antigen and enhanced testosterone-induced reduction of androgen receptor mRNA expression. Following 38 hours of testosterone treatment cell morphology changed and growth declined; however, cotreatment with SHBG abrogated these inhibitory effects. These findings clearly demonstrate that internalised SHBG plays an important regulatory and intracellular role in modifying testosterone action and this has important implications for the role of SHBG in health and disease."

Also, notice that they added SHBG!  Maybe I am missing something, but it sounds like SHBG could be compounded and given to men just like testosterone or the hormones?

Anyway, I will probably incur the wrath of some of the low SHBG guys on here, but I think that most low SHBG guys often struggle and quite often react badly to TRT.  I think this explains what is going on there.

Check out my pages on low SHBG if you are interested:

http://www.peaktestosterone.com/low_shbg.aspx
THE MOST COMPREHENSIVE BOOK ON TRT/TESTOSTERONE:
https://www.amazon.com/Natural-Versus-Testosterone-Therapy-Myer/dp/1523210532/ref=sr_1_1?ie=UTF8&qid=1499116128&sr=8-1&keywords=natural+versus+testosterone+therapy
And check out my New Peak Testosterone Program: http://www.peaktestosterone.com/peak_testosterone_program.aspx
If you are on medications or have a medical condition, always check with your doctor first before making any lifestyle changes or taking new supplements.  And low testosterone is a medical condition.

Peak Testosterone Forum

Re: SHBG Controls Androgens (Testosterone, etc.) Inside the Cell!
« Reply #3 on: January 11, 2018, 05:09:24 am »


PeakT

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Re: SHBG Controls Androgens (Testosterone, etc.) Inside the Cell!
« Reply #4 on: January 11, 2018, 05:25:59 am »

https://www.ncbi.nlm.nih.gov/m/pubmed/16143106/

Full text:
 http://www.cell.com/cell/fulltext/S0092-8674(05)00651-3?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867405006513%3Fshowall%3Dtrue

Androgens and estrogens are transported bound to the sex hormone binding globulin (SHBG). SHBG is believed to keep sex steroids inactive and to control the amount of free hormones that enter cells by passive diffusion. Contrary to the free hormone hypothesis, we demonstrate that megalin, an endocytic receptor in reproductive tissues, acts as a pathway for cellular uptake of biologically active androgens and estrogens bound to SHBG. In line with this function, lack of receptor

In line with this function, lack of receptor expression in megalin knockout mice results in impaired descent of the testes into the scrotum in males and blockade of vagina opening in females. Both processes are critically dependent on sex-steroid signaling, and similar defects are seen in animals treated with androgen- or estrogen-receptor antagonists.

Would you mind if I merged this with your last post?  Did you notice I stickied it and put it at the top of the forum?  Incredibly important stuff and thx for the research.
THE MOST COMPREHENSIVE BOOK ON TRT/TESTOSTERONE:
https://www.amazon.com/Natural-Versus-Testosterone-Therapy-Myer/dp/1523210532/ref=sr_1_1?ie=UTF8&qid=1499116128&sr=8-1&keywords=natural+versus+testosterone+therapy
And check out my New Peak Testosterone Program: http://www.peaktestosterone.com/peak_testosterone_program.aspx
If you are on medications or have a medical condition, always check with your doctor first before making any lifestyle changes or taking new supplements.  And low testosterone is a medical condition.

doin it

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Re: SHBG Controls Androgens (Testosterone, etc.) Inside the Cell!
« Reply #5 on: January 11, 2018, 07:12:40 am »

You are welcome, Peak.

Yes, you may merge if you like.  If you would, please delete the last sentence in the first paragraph "In line with this function, lack of receptor"as it is redundant to the first sentence in the second patagraph.

Thanks


PeakT

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Re: SHBG Controls Androgens (Testosterone, etc.) Inside the Cell!
« Reply #6 on: January 11, 2018, 08:00:36 am »

You are welcome, Peak.

Yes, you may merge if you like.  If you would, please delete the last sentence in the first paragraph "In line with this function, lack of receptor"as it is redundant to the first sentence in the second patagraph.

Thanks

Done.  Again, great info and I think a lot of important things will spring out of this line of reserach.  I think this will help guys feel a lot better and also help them to find out in some cases why they don't feel good in the first place.

Hey, can you do that edit?  I was a little confused what you wanted me to do, and I don't want to clobber something you said.
THE MOST COMPREHENSIVE BOOK ON TRT/TESTOSTERONE:
https://www.amazon.com/Natural-Versus-Testosterone-Therapy-Myer/dp/1523210532/ref=sr_1_1?ie=UTF8&qid=1499116128&sr=8-1&keywords=natural+versus+testosterone+therapy
And check out my New Peak Testosterone Program: http://www.peaktestosterone.com/peak_testosterone_program.aspx
If you are on medications or have a medical condition, always check with your doctor first before making any lifestyle changes or taking new supplements.  And low testosterone is a medical condition.

Dr. John Crisler

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Re: SHBG Controls Androgens (Testosterone, etc.) Inside the Cell!
« Reply #7 on: January 11, 2018, 08:26:45 pm »
We keep getting closer to explaining the tough cases.
Physician in Age Management Medicine private practice. www.DrJohnCrisler.com

NOTE: Comments on this forum are NOT medical advice and are no substitute for individualized patient care. Please consult your personal physician prior to initiating or changing ANY treatment regimen.

Dr Justin Saya, MD

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Re: SHBG Controls Androgens (Testosterone, etc.) Inside the Cell!
« Reply #8 on: January 11, 2018, 09:35:37 pm »
We keep getting closer to explaining the tough cases.

Indeed...understanding the full complexity of the MOA of SHBG - both extracellular and INTRAcellular (which doesn't show on lab testing btw) - along with (in my opinion another complicating variable in tough cases) variations in the CAG repeat sequence of the androgen receptor is part of the next frontier of HRT/TRT.
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http://www.defymedical.com

NOTE: Comments on this forum are NOT medical advice and are no substitute for individualized patient care. Comments on this forum do not constitute or establish a physician-patient relationship. Please consult your personal physician prior to initiating or changing ANY treatment regimen.

PeakT

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Re: SHBG Controls Androgens (Testosterone, etc.) Inside the Cell!
« Reply #9 on: January 11, 2018, 10:23:17 pm »


Indeed...understanding the full complexity of the MOA of SHBG - both extracellular and INTRAcellular (which doesn't show on lab testing btw) - along with (in my opinion another complicating variable in tough cases) variations in the CAG repeat sequence of the androgen receptor is part of the next frontier of HRT/TRT.

Yeah, we have one man on here (BBBluesKing) who has been bombarding us (in a good way) with studies on the CAG repeat issue.  I have been a little skeptical of personalized medicine, but I read things like that and it makes me a believer.
THE MOST COMPREHENSIVE BOOK ON TRT/TESTOSTERONE:
https://www.amazon.com/Natural-Versus-Testosterone-Therapy-Myer/dp/1523210532/ref=sr_1_1?ie=UTF8&qid=1499116128&sr=8-1&keywords=natural+versus+testosterone+therapy
And check out my New Peak Testosterone Program: http://www.peaktestosterone.com/peak_testosterone_program.aspx
If you are on medications or have a medical condition, always check with your doctor first before making any lifestyle changes or taking new supplements.  And low testosterone is a medical condition.

charliebizz

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Re: SHBG Controls Androgens (Testosterone, etc.) Inside the Cell!
« Reply #10 on: January 12, 2018, 01:57:40 pm »
Serious question for the docs. So what is a guy like me with low shbg who isnít seeing much improvement from trt at the moment do for the time being. Is it still truly worth being on trt. Is it still doing things for my health that I might not see. This is all assuming Iím on the best available program at the moment. 

Iím not even saying for me cause I still probably havenít been on long enough. But for the guys who feel as though they are injecting water?

PeakT

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Re: SHBG Controls Androgens (Testosterone, etc.) Inside the Cell!
« Reply #11 on: January 12, 2018, 06:03:51 pm »
Serious question for the docs. So what is a guy like me with low shbg who isnít seeing much improvement from trt at the moment do for the time being. Is it still truly worth being on trt. Is it still doing things for my health that I might not see. This is all assuming Iím on the best available program at the moment. 

Iím not even saying for me cause I still probably havenít been on long enough. But for the guys who feel as though they are injecting water?

You probably want to ask that separately.
THE MOST COMPREHENSIVE BOOK ON TRT/TESTOSTERONE:
https://www.amazon.com/Natural-Versus-Testosterone-Therapy-Myer/dp/1523210532/ref=sr_1_1?ie=UTF8&qid=1499116128&sr=8-1&keywords=natural+versus+testosterone+therapy
And check out my New Peak Testosterone Program: http://www.peaktestosterone.com/peak_testosterone_program.aspx
If you are on medications or have a medical condition, always check with your doctor first before making any lifestyle changes or taking new supplements.  And low testosterone is a medical condition.

Dr. John Crisler

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Re: SHBG Controls Androgens (Testosterone, etc.) Inside the Cell!
« Reply #12 on: January 14, 2018, 07:26:42 pm »
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136390/
(
Sex Hormone Binding Globulin (SHBG) is the major serum carrier of sex hormones. However, growing evidence suggests that SHBG is internalised and plays a role in regulating intracellular hormone action. This study was to determine whether SHBG plays a role in testosterone uptake, metabolism, and action in the androgen sensitive LNCaP prostate cancer cell line.

Oh my goodness, what a gem.  This explains a heck of a lot in my opinion.

The thesis of this article is that you need SHBG INSIDE your cells for protection and inhibition of androgens.  Check out this statement:

"Testosterone was rapidly taken up and effluxed as testosterone-glucuronide; however this effect was reduced by the presence of SHBG. Addition of SHBG, rather than reducing testosterone bioavailability, further increased testosterone-induced expression of prostate specific antigen and enhanced testosterone-induced reduction of androgen receptor mRNA expression. Following 38 hours of testosterone treatment cell morphology changed and growth declined; however, cotreatment with SHBG abrogated these inhibitory effects. These findings clearly demonstrate that internalised SHBG plays an important regulatory and intracellular role in modifying testosterone action and this has important implications for the role of SHBG in health and disease."

Also, notice that they added SHBG!  Maybe I am missing something, but it sounds like SHBG could be compounded and given to men just like testosterone or the hormones?

Anyway, I will probably incur the wrath of some of the low SHBG guys on here, but I think that most low SHBG guys often struggle and quite often react badly to TRT.  I think this explains what is going on there.

Check out my pages on low SHBG if you are interested:

http://www.peaktestosterone.com/low_shbg.aspx
I have found men who suffer anxiety are likely to have low(er) SHBG.

And they are less likely (although--as always--everybody is different) to do well on a TD. It is as if they cannot tolerate the wide swings in serum hormone levels; the same variability which is usually good for you. As I always say:

Entropy is part and parcel of youth.
Physician in Age Management Medicine private practice. www.DrJohnCrisler.com

NOTE: Comments on this forum are NOT medical advice and are no substitute for individualized patient care. Please consult your personal physician prior to initiating or changing ANY treatment regimen.

Dr Justin Saya, MD

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Re: SHBG Controls Androgens (Testosterone, etc.) Inside the Cell!
« Reply #13 on: January 15, 2018, 05:16:13 pm »
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136390/
(
Sex Hormone Binding Globulin (SHBG) is the major serum carrier of sex hormones. However, growing evidence suggests that SHBG is internalised and plays a role in regulating intracellular hormone action. This study was to determine whether SHBG plays a role in testosterone uptake, metabolism, and action in the androgen sensitive LNCaP prostate cancer cell line.

Oh my goodness, what a gem.  This explains a heck of a lot in my opinion.

The thesis of this article is that you need SHBG INSIDE your cells for protection and inhibition of androgens.  Check out this statement:

"Testosterone was rapidly taken up and effluxed as testosterone-glucuronide; however this effect was reduced by the presence of SHBG. Addition of SHBG, rather than reducing testosterone bioavailability, further increased testosterone-induced expression of prostate specific antigen and enhanced testosterone-induced reduction of androgen receptor mRNA expression. Following 38 hours of testosterone treatment cell morphology changed and growth declined; however, cotreatment with SHBG abrogated these inhibitory effects. These findings clearly demonstrate that internalised SHBG plays an important regulatory and intracellular role in modifying testosterone action and this has important implications for the role of SHBG in health and disease."

Also, notice that they added SHBG!  Maybe I am missing something, but it sounds like SHBG could be compounded and given to men just like testosterone or the hormones?

Anyway, I will probably incur the wrath of some of the low SHBG guys on here, but I think that most low SHBG guys often struggle and quite often react badly to TRT.  I think this explains what is going on there.

Check out my pages on low SHBG if you are interested:

http://www.peaktestosterone.com/low_shbg.aspx
I have found men who suffer anxiety are likely to have low(er) SHBG.

And they are less likely (although--as always--everybody is different) to do well on a TD. It is as if they cannot tolerate the wide swings in serum hormone levels; the same variability which is usually good for you. As I always say:

Entropy is part and parcel of youth.

Entropy is, quite literally, part and parcel of the universe!
Lead Physician & Medical Director
http://www.defymedical.com

NOTE: Comments on this forum are NOT medical advice and are no substitute for individualized patient care. Comments on this forum do not constitute or establish a physician-patient relationship. Please consult your personal physician prior to initiating or changing ANY treatment regimen.

Dr. John Crisler

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Re: SHBG Controls Androgens (Testosterone, etc.) Inside the Cell!
« Reply #14 on: January 16, 2018, 05:29:17 am »
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136390/
(
Sex Hormone Binding Globulin (SHBG) is the major serum carrier of sex hormones. However, growing evidence suggests that SHBG is internalised and plays a role in regulating intracellular hormone action. This study was to determine whether SHBG plays a role in testosterone uptake, metabolism, and action in the androgen sensitive LNCaP prostate cancer cell line.

Oh my goodness, what a gem.  This explains a heck of a lot in my opinion.

The thesis of this article is that you need SHBG INSIDE your cells for protection and inhibition of androgens.  Check out this statement:

"Testosterone was rapidly taken up and effluxed as testosterone-glucuronide; however this effect was reduced by the presence of SHBG. Addition of SHBG, rather than reducing testosterone bioavailability, further increased testosterone-induced expression of prostate specific antigen and enhanced testosterone-induced reduction of androgen receptor mRNA expression. Following 38 hours of testosterone treatment cell morphology changed and growth declined; however, cotreatment with SHBG abrogated these inhibitory effects. These findings clearly demonstrate that internalised SHBG plays an important regulatory and intracellular role in modifying testosterone action and this has important implications for the role of SHBG in health and disease."

Also, notice that they added SHBG!  Maybe I am missing something, but it sounds like SHBG could be compounded and given to men just like testosterone or the hormones?

Anyway, I will probably incur the wrath of some of the low SHBG guys on here, but I think that most low SHBG guys often struggle and quite often react badly to TRT.  I think this explains what is going on there.

Check out my pages on low SHBG if you are interested:

http://www.peaktestosterone.com/low_shbg.aspx
I have found men who suffer anxiety are likely to have low(er) SHBG.

And they are less likely (although--as always--everybody is different) to do well on a TD. It is as if they cannot tolerate the wide swings in serum hormone levels; the same variability which is usually good for you. As I always say:

Entropy is part and parcel of youth.

Entropy is, quite literally, part and parcel of the universe!
Well said.

As we age, hormone levels may fluctuate even to the same peaks and valleys, but the intervals can become longer. That means a given hormone's concentration may be at each level the same amount of time each day--but health and happiness decreases.

This shows how the shape of the hormone profile is an important part of the information hormones transmit. Their signalling is not just on/off, or even concentration.

Indeed, we have seen how rapid accelerations in hormone levels change enzyme activity, urinary excretion, and subjective report (how they feel) from patients.
Physician in Age Management Medicine private practice. www.DrJohnCrisler.com

NOTE: Comments on this forum are NOT medical advice and are no substitute for individualized patient care. Please consult your personal physician prior to initiating or changing ANY treatment regimen.

Peak Testosterone Forum

Re: SHBG Controls Androgens (Testosterone, etc.) Inside the Cell!
« Reply #14 on: January 16, 2018, 05:29:17 am »