Sex Hormone Binding Globulin [SHBG]

[Michael Scally MD]

Highlights
· We analyzed the relationship of SHBG gene polymorphisms and BMD in Chinese men.
· SHBG gene polymorphisms is related to BMD and osteoporosis.
· Haplotype CCGGT and CGGT was associated with a significant risk effect for osteoporosis.

Zha X-Y, Hu Y, Pang X-N, Zhu J-H, Chang G-L, Li L. The association between sex hormone-binding globulin gene polymorphism with bone mineral density. Steroids. The association between sex hormone-binding globulin gene polymorphism with bone mineral density

To investigate the impact of single nucleotide polymorphisms(SNPs) of SHBG gene the neighboring genes on SHBG levels, bone mineral density(BMD) and osteoporosis in Chinese males. A group of Chinese men, aged >/= 45 years were included in the analysis.

BMD was measured with dual-energy x-ray absorptiometry (DXA), SHBG and total testosterone(TT) was measured using chemiluminescent immunoassay, and free testosterone(FT) was calculated. SNPs of SHBG gene and the neighboring genes were studied by means of improved multiple ligase detection reaction (iMLDR).

A total of 404 men were included in our study. In the single locus analysis, significant associations were found between SHBG levels and four polymorphisms (rs11078701, rs9901675, rs9898876 and rs2541012) in age- and BMI-adjusted models. In addition, statistically significant difference was found between osteoporosis patients and control subjects in genotype distributions of rs9898876, rs2541012, rs6259 and rs3853894.

In the models with or without adjustment for confounders (age, BMI, SHBG and free testosterone (FT) levels), carriers of variant genotype of rs9898876, rs2541012 and rs6259 had lower BMD and were more likely to suffer from osteoporosis, as compare to carriers of common genotype.

Subjects with variant genotype of rs3853894 had higher BMD and were less likely to suffer from osteoporosis, as compared to subjects with common genotype. In the haplotypes analysis, CCGGT(constituted by rs11078701C, rs1017163C, rs9898876G, rs62059836G and rs2541012T) and haplotype CGGT(constituted by rs858521C, rs858518G, rs6259G and rs727428T) was associated with a significant risk effect for osteoporosis.

Polymorphisms of SHBG or the neighboring genes were associated with SHBG levels or BMD and osteoporosis, suggesting the involvement of genetic variation of SHBG in bone health.

 

[hardrlz]

So if its genetic are we basically screwed for life ?

 

[James23]

There might be some hope with the upcoming drug Capesaris.

 

[hardrlz]

Thats interesting, i would be willing to test this if i could get my hands on it, maybe there is a way to obtain it before it comes to market ?

 

[Michael Scally MD]

Sex Hormones, Sex Hormone Binding Globulin, and Vertebral Fractures

Highlights

• Higher SHBG (but not testosterone or estradiol) is an independent risk factor for vertebral fractures in older men.

The association between sex hormones and sex hormone binding globin (SHBG) with vertebral fractures in men is not well studied. In these analyses, we determined whether sex hormones and SHBG were associated with greater likelihood of vertebral fractures in a prospective cohort study of community dwelling older men.

We included data from participants in MrOS who had been randomly selected for hormone measurement (N=1463 including 1054 with follow-up data 4.6years later.). Major outcomes included prevalent vertebral fracture (semi-quantitative grade>/=2, N=140, 9.6%); and new or worsening vertebral fracture (change in SQ grade>/=1, N=55, 5.2%).

Odds ratios per SD decrease in sex hormones and per SD increase in SHBG were estimated with logistic regression adjusted for potentially confounding factors including age, bone mineral density, and other sex hormones.

Higher SHBG was associated with a greater likelihood of prevalent vertebral fractures (OR: 1.38 per SD increase, 95% CI: 1.11, 1.72).

Total estradiol analyzed as a continuous variable was not associated with prevalent vertebral fractures (OR per SD decrease: 0.86, 95% CI: 0.68 to 1.10). Men with total estradiol values </=17pg/ml had a borderline higher likelihood of prevalent fracture than men with higher values (OR: 1.46, 95% CI: 0.99, 2.16).

There was no association between total testosterone and prevalent fracture.

In longitudinal analyses, SHBG (OR: 1.42 per SD increase, 95% CI: 1.03, 1.95) was associated with new or worsening vertebral fracture, but there was no association with total estradiol or total testosterone.

In conclusion, higher SHBG (but not testosterone or estradiol) is an independent risk factor for vertebral fractures in older men.

Cawthon PM, Schousboe JT, Harrison SL, et al. Sex hormones, sex hormone binding globulin, and vertebral fractures in older men. Bone. https://www.sciencedirect.com/science/article/pii/S8756328216000107

 

[Michael Scally MD]

Effects Of Sex Hormone-Binding Globulin (SHBG) On Androgen Bioactivity In Vitro

Highlights
· An androgen receptor, androgen response element luciferase bioassay was established
· Sex hormone-binding globulin (SHBG) suppressed androgen bioactivity in vitro
· Bioassay results are sensitive to dilution effects in an SHBG-dependent manner
· Anti-androgens, androgen deprivation or replacement therapy influenced bioactivity

Biochemical assessments of androgen status (hyper- or hypoandrogenism) are usually based on serum testosterone concentrations. According to the free hormone hypothesis, sex hormone-binding globulin (SHBG) determines free and bioavailable testosterone concentrations. Previous studies have suggested that in vitro androgen bioassay results may also be influenced by SHBG and correlate with free or bioavailable testosterone concentrations.

To test this hypothesis, we established a stable HEK293 cell line with high expression of the human androgen receptor (AR) and a luciferase reporter downstream of a classical androgen response element. Importantly, we demonstrate that bioassay results are sensitive to dilution effects which increase apparent bioactivity in an SHBG-dependent manner. We therefore adopted a method using undiluted serum, which reduced cell proliferation but did not significantly affect the luciferase signal, cell viability or cytotoxicity.

To correct for serum matrix effects, we applied signal correction based on internal controls with AR agonists or antagonists. Using this method, we provide direct evidence that in vitro androgen bioactivity reflects the inhibitory effects of SHBG, and correlates with free or bioavailable testosterone concentrations in adult hypogonadal men receiving androgen replacement therapy.

In men receiving anti-androgens, serum bioactivity decreased tenfold while serum testosterone concentrations decreased only four-fold. Further pilot results in prostate cancer patients showed that androgen synthesis inhibitors result in more complete inhibition of androgen bioactivity than gonadorelin-based androgen deprivation therapy, even in patients whose testosterone concentrations were undetectable by mass spectrometry.

We conclude that in vitro androgen reporter bioassays are useful tools to study how androgen bioactivity in serum is determined by androgens, anti-androgens as well as SHBG, provided that dilution and matrix effects are accounted for.

Laurent MlR, Helsen C, Antonio L, et al. Effects of sex hormone-binding globulin (SHBG) on androgen bioactivity in vitro. Molecular and Cellular Endocrinology. Effects of sex hormone-binding globulin (SHBG) on androgen bioactivity in vitro

 

[Tyler81]

I have low SHBG and the only form of TRT that works for me is the transdermals.

When i do injections I get bad anxiety and moodyness which I think is my free T spiking too high. Prop is better than cyp. But gels are the best form of TRT for me but they have stopped absorbing.

The CAUSE of low SHBG is key and i think i have type 2 diabetes (or borderline) and I am going to look into treating that.

If I could get my SHBG to improve by treating my high blood sugar (including diet) then I maybe T injections would work for me re: my free T wouldnt spike so high and i wouldnt feel shitty for 2-3 days after each injection.

 

[Tyler81]

These two snippets from studies indicate that SHBG does more than "bind" T.

It acts as a "reservoir for androgens that can be accessed by the AR"
and, "intracellular SHBG accentuates the uptake of androgens and sustains access to the androgen receptor.

Sex hormone-binding globulin (SHBG) is the high-affinity plasma transport protein for androgens and estrogens, and it modulates the amounts of free or nonprotein- bound sex steroids that can access their target tissues. The presence of human SHBG within cells raises the obvious question of whether it promotes the internalization and actions of sex steroids, or dampens their effects by restricting steroid access to their nuclear receptors.These questions were explored in a series of experiments that lead researchers to conclude that the presence of human SHBG within specific cell types, such as pct epithelial cells, accentuates the uptake of androgens and serves as a reservoir for androgens that can be accessed by the AR, and that this may be especially important under conditions where the supply of androgens is limited.

Mol Endocrinol. 2010 Dec 30;

Authors: Hong EJ, Sahu B, Jänne OA, Hammond GL
Thus, intracellular SHBG accentuates the uptake of androgens and sustains androgens access to the androgen receptor, especially under conditions of limited androgen supply.

 

[InfoFront]

I'm in the same boat as you. I'm a low SHBG guy with no libido. I've tried many, many drugs, supplements, etc. and few things have had any effect. The ones that have are strong androgens - trenbolone and high dose proviron, but the side effects are too much for me.
One thing I'm curious about is bremelanotide (sp?). Ever tried it?

 

[James23]

I'm in the same boat as you. I'm a low SHBG guy with no libido. I've tried many, many drugs, supplements, etc. and few things have had any effect. The ones that have are strong androgens - trenbolone and high dose proviron, but the side effects are too much for me.
One thing I'm curious about is bremelanotide (sp?). Ever tried it?

Bremelanotide, I have not officially tried. I did give it a run about ten years ago in nasal spray form. My face turned red and my heartbeat accelerated. I did get erections out of it, but the Viagra kind... not the aroused kind. I don't agree that it bremelanotide has anything to do with libido.

 

[Tyler81]

I have been prescribed Metformin for insulin resistance.
Has anyone taken Metformin and measured their before and after SHBG?

 

[BBC3]

Tyler, its funny you bring this up today as one of my reasons for visiting the forum lately is that an older friend of mine was prescribed metformin about a month ago and hes not looking so hot. He has a myriad of health issues any hard worked 75 year old man might expect to see and along with other issues like a couple of bypasses now, etc. But the guy is fit as hell, and was a bright and energetic as anyone can be at any age. This week he reported he has been sluggish and was even slurring the other morning and not looking so hot. It seems like in my experience meeting folks and family who has used this drug as a front line approach to Type II diabetes all wind up getting messed up and/or have serious issues that seem to be related to the metformin.??? In short I joked for a long time that every older person I have met who has been prescribed Metformin lated in life "got took out by it in some way related"...

I once knew a little about the drug and actually experimented with it as a booster for body fat reduction while working out seriously. I recall quitting the drug after about 6 weeks as the effect of body fat reduction I was looking for in a body not having diabetes conditions, was too minimal to make it worth taking.

The primary risk associated it seems like I recall was some kind of blood ketone acidosis or i think technically "ketoacidosis (DKA)?" and while i research that this is a condition which accompanies diabetes many times, I DO BELIEVE the condition was actually stated as CAUSED BY metformin as a side effect to anyone using the drug. I could be wrong but in seems like I also read that in the literature on metformin way back.?!? I did have some muscular burning sensations in lower legs similar to a post workout burn as if returning to training after not working out for a long period. Which was not the case as I was fully trained when I started the drug. So that prompted my research at the time.

Its also funny as I just stumbled on some info about invokana (current new oral diabetes med), which i believe reads like it treats ketoacidosis (DKA)? So that has me confused now.

And so as not to totally hijack. It does math out that as all these blood factors correlate, that if you took a drug which bolstered insulin response, you would have a change in SHBG as more available protein at the cell, would require more hormones at the cell to metabolize it. However those DAMN serum counts.. LOL But WHAT? It would of course require more SHBG but would this in fact expedite the use of a POSSIBLY SET SUPPLY or 'temporarily set-pointed" SHBG level, and thus lower SHBG levels visible in serum as now the SHBG was being more readily metabolized...??

*** And again, are we measuring "Free" SHBG in this serum measurement? Or all SHBG present in blood as also what is occupied by working cells currently as well. The later would of course mean an ultimate higher SHBG count most likely.. Did we ever get to the bottom of that question..?

But anyone knowledgeable regarding Metformin please reply or PM me and let me know should this friend of mine be concerned about the lethargy he is experiencing one month into his new Metformin Protocol..?? I believe it was a blood sugar count of 296 on a CBC (no detailed technical testing like insulin stress test at this time) which prompted the prescription by which ever doc directed it..

And here is the data about "DKA" which invokana publishes in their front line advertising...

(And I stand corrected as Invokana and Invokamet is advertising Ketoacidosis as a side effect to this drug too).

"important safety information
When you’re considering a new medication, understanding the side effects can be just as important as understanding the benefits.

Below are some of the side effects that have been reported with INVOKAMET®, followed by the Important Safety Information:

(is "Invokamet" even the same drug as Invokana - DAMN!?!?!?!)
YES (they are both canagliflozin...) CRAP..!!

• Dehydration due to the loss of body water and salt
• Kidney problems
• Vaginal yeast infection
• Yeast infection of the penis
• Ketoacidosis
• Risk of bone fracture
• Potentially serious urinary tract infection
• Changes in urination, including the urgent need to urinate more often, in larger amounts, or at night
• High potassium in the blood (hyperkalemia)
• Low blood sugar (hypoglycemia)
• Increases in cholesterol"

And more...

Lactic Acidosis. Metformin, one of the medicines in INVOKAMET®, can cause a rare but serious condition called lactic acidosis (a build-up of lactic acid in the blood) that can cause death. Lactic acidosis is a medical emergency and must be treated in the hospital. Call your doctor right away if you have any of the following symptoms which could be signs of lactic acidosis: feel cold in your hands or feet; feel very weak or tired; have unusual (not normal) muscle pain; have trouble breathing; have unusual sleepiness or sleep longer than usual; have stomach pains, nausea, or vomiting; feel dizzy or lightheaded; or have a slow/irregular heartbeat

!!!!! That answers some of my questions about the guy as he has many of these symptoms..! the guy told me he though he was having heart trouble and has scheduled an appt with cardiologist stating he was skipping a beat every 5-10 beats or so...

Lastly Tyler. I am not up to speed with this thread So I am not sure what you are after specifically and apologize i dont have time to contribute more right now. But thanks to your post, I am extremely concerned about this older fella friend of mine and conveying the information that you prompted me to look up. He may need to contact his doc immediate. These side effects of related to Lactic acidosis are frighteningly similar to what was going on with my friend yesterday and a month into his metformin script.

thx..!

I have been prescribed Metformin for insulin resistance.
Has anyone taken Metformin and measured their before and after SHBG?

 

[hardasnails1973]

when working with clients using metformin some tend to see a drop in b12 serums as well as altering methylmalonic acid. These levels may not have been an issue before, but may be one now. It also can deplete folic acid as well as a few others minerals. It also can cause in some people mitochondrion damage specifically in complex i as well as lactic acidosis as previously mentioned. It would be suggested to be properly evalUated by a medical professional to confirm the situation.

 

[James23]

*** And again, are we measuring "Free" SHBG in this serum measurement? Or all SHBG present in blood as also what is occupied by working cells currently as well. The later would of course mean an ultimate higher SHBG count most likely.. Did we ever get to the bottom of that question..?

We are measuring all SHBG present in the blood.

 

[Tyler81]

BBC AND HANS make a return to the forum to reply to my Metformin inquiry lol

BBC where the hell have ya been? This forum has been dry without your posts !

 

[hardasnails1973]

Tyler, don't you feel the bromance in the air LOL

 

[BBC3]

Thank you. But at which time does an "SHBG" become whatever hormone and no longer and SHBG ATTACHED to a hormone.?? Again, are we measuring "Free SHBG" ,,, OR ,,, At what stage and for how long can SHBG STILL BE IDENTIFIED as an independent component.??

1. While attached to a hormone and UNTIL it reaches a receptor.??
2. Only until it involves with a hormone and not after, ever...?
3. Are there any conditions in which SHBG goes on to be recycled and re-used for its job?
4. Have you ever looked at the complex MOLARITY/MOLALITY Equation associated with SHBG? Have you worked the math?
5. What are the "NATURAL SHBG KILLERS". Do they exists..?
6. What's the lifespan of a SHBG if remaining unused.?
7. What are the CONSEQUENCES to an unused SHBG?
8. If SHBG is STILL IDENTIFIABLE TO THE BODY after incorporation with a HORMONE. If affecting any internal regulators to new production.
9. Does an E2 converted to an E3 travel on to the next receptor via the same SHBG. Or DOES E3 only affect the cell at which the E2 hence metabolized to SAID..?
10. Does E2 (or any estrogen for that matter) always have a $ for $ dollar production rate. IS ONLY ONE E3 produced for ONE E2...?!
11. In muti-faceted tissue cells which accept either E OR T/A, what is the HOLDING FACTOR.. And WHAT FORCES THE RELEASE...!
12. What is the lifespan of E2 vs. E3 vs. T or Androgens..? And what are the physical factors regulating this?
How does albumin presence in the blood relate? After all abumin is the "other half" we never speak of... What is the true mission of ALBUMIN.. How does it relate..?
13. Is SHBG production driven by available hormones PRODUCED, OR Cellular DEmand for hormones...
14. How do other liver products affect these factors. So many variables.
15. SHBG is a GLYCOPROTIEN. What other blood conditions can affect..?
16. How does caloric food intake affect SHBG? Can it be eaten by HUNGRY CELLS in a strained environment.
17. I recently read people anecdotally citing that use of liver metabolized drugs, including alcohol can reduce testosterone up to 40% in a matter of days..??!? Is this true do you think?
18. What GENERAL CONDITIONS affect SHBG among other liver produced actors..?
19. How do ENDOCRINE DISRUPTORS PLAY IN...!!?? This is real and unspoken. I also suspect that BPA is simply a disctraction from the the real villain - Pthylates. Which are much more common, potentially potent, and still in disguise by current social standards.
20. Do endocrine disruptors, LIKE PLASTICIZERS as mentioned above, affect the liver or the HORMONE, or the BRAIN...?!? Or all of the above... They say gas station receipts notoriously have 1000 times the safe level of BPA in component....
21. Are we ALL JUST LAB RATS or targeted for termination in this event call life governed by so many forces unseen and unpredicted...
22. WHY is SHBG and ALBUMIN such a fuking mystery..?? Why... And why does science simply not provide any real laymonizing analysis for the general public. And when they know so well...
23. Most importantly - WHY IS THERE NOT A PUBLIC SOURCE FOR GENERAL PUBLIC INFORMATION/Laymanization OF THE DISSEMINATION OF ALL THIS DATA..
24. And finally, when you consider when you look at space from a clear sky in Montana, and can see the whole fuking Milky Way. WHY IS THERE NOT ONE GOD DAMN PHOTO FROM ORBIT OR ANY TIME NASA IS IN SPACE THAT SHOWS ANYTHING OTHER THAN A FEW TWINKLING STARS IN THE DISTANCE. And when there should be all that much more visible. More than ever possibly visible from Earth's surface... Must be a real collidescope... I COULD IMAGINE.....!

We are measuring all SHBG present in the blood.

 

[BBC3]

I discussed this with an astute internal buddy of mine (who remains unaware and uninvolved with my quest here. NOR does he really talk shop with me. We have OTHER ENDEAVORS TO PURSUE ...

Anywayz, he stated he's done the bloodwork for blood acid conditions potentially associated with Metformin a bazillion time and always comes up snake eyes...

My friend which I was inquiring about is scheduled to go into hospital today and have a cath proceedure done to go up in his heart and examine the many stents and previous bypass surgery's current conditions and status. He was chipper today and I feel like whatever was going on was temporary and most likely related to his heart history. just a bad moment. WE WILL SEE..

But I did ask him did he inform all docs he was on metformin for last months and have they acknowledged and he states yes... So perhaps more than he has told me.. I prey for my friends always..

Thank you for the reply..!

when working with clients using metformin some tend to see a drop in b12 serums as well as altering methylmalonic acid. These levels may not have been an issue before, but may be one now. It also can deplete folic acid as well as a few others minerals. It also can cause in some people mitochondrion damage specifically in complex i as well as lactic acidosis as previously mentioned. It would be suggested to be properly evalUated by a medical professional to confirm the situation.

 

[BBC3]

LASTLY I WILL ADD AND WITH ALL THE DATA WE HAVE. Has SHBG ever been looked at closely enough to determine is there is some FUNDAMENTAL FAILURE of SHBG as produced by the liver, in that COULD IT POSSIBLY ATTACH TO HORMONES, but in ways that don't totally enable hormone delivery to said receptor cells, YET "De-Qualify" said hormone to be an active asset from there on. Essentially creating and rendering "High Cost Waste on Waste"... A complete waste...?!>? Is there a such a thing as a failed SHBG? and What Else could potentially cause this to happen..? Blood PH..? Chemical/biological. Is it a simple answer to our current biological intake and stimulus...??? WHAT IS the correct PH of the Blood in OPTIMAL CONDITIONS...?!

Thank you. But at which time does an "SHBG" become whatever hormone and no longer and SHBG ATTACHED to a hormone.?? Again, are we measuring "Free SHBG" ,,, OR ,,, At what stage and for how long can SHBG STILL BE IDENTIFIED as an independent component.??

1. While attached to a hormone and UNTIL it reaches a receptor.??
2. Only until it involves with a hormone and not after, ever...?
3. Are there any conditions in which SHBG goes on to be recycled and re-used for its job?
4. Have you ever looked at the complex MOLARITY/MOLALITY Equation associated with SHBG? Have you worked the math?
5. What are the "NATURAL SHBG KILLERS". Do they exists..?
6. What's the lifespan of a SHBG if remaining unused.?
7. What are the CONSEQUENCES to an unused SHBG?
8. If SHBG is STILL IDENTIFIABLE TO THE BODY after incorporation with a HORMONE. If affecting any internal regulators to new production.
9. Does an E2 converted to an E3 travel on to the next receptor via the same SHBG. Or DOES E3 only affect the cell at which the E2 hence metabolized to SAID..?
10. Does E2 (or any estrogen for that matter) always have a $ for $ dollar production rate. IS ONLY ONE E3 produced for ONE E2...?!
11. In muti-faceted tissue cells which accept either E OR T/A, what is the HOLDING FACTOR.. And WHAT FORCES THE RELEASE...!
12. What is the lifespan of E2 vs. E3 vs. T or Androgens..? And what are the physical factors regulating this?
How does albumin presence in the blood relate? After all abumin is the "other half" we never speak of... What is the true mission of ALBUMIN.. How does it relate..?
13. Is SHBG production driven by available hormones PRODUCED, OR Cellular DEmand for hormones...
14. How do other liver products affect these factors. So many variables.
15. SHBG is a GLYCOPROTIEN. What other blood conditions can affect..?
16. How does caloric food intake affect SHBG? Can it be eaten by HUNGRY CELLS in a strained environment.
17. I recently read people anecdotally citing that use of liver metabolized drugs, including alcohol can reduce testosterone up to 40% in a matter of days..??!? Is this true do you think?
18. What GENERAL CONDITIONS affect SHBG among other liver produced actors..?
19. How do ENDOCRINE DISRUPTORS PLAY IN...!!?? This is real and unspoken. I also suspect that BPA is simply a disctraction from the the real villain - Pthylates. Which are much more common, potentially potent, and still in disguise by current social standards.
20. Do endocrine disruptors, LIKE PLASTICIZERS as mentioned above, affect the liver or the HORMONE, or the BRAIN...?!? Or all of the above... They say gas station receipts notoriously have 1000 times the safe level of BPA in component....
21. Are we ALL JUST LAB RATS or targeted for termination in this event call life governed by so many forces unseen and unpredicted...
22. WHY is SHBG and ALBUMIN such a fuking mystery..?? Why... And why does science simply not provide any real laymonizing analysis for the general public. And when they know so well...
23. Most importantly - WHY IS THERE NOT A PUBLIC SOURCE FOR GENERAL PUBLIC INFORMATION/Laymanization OF THE DISSEMINATION OF ALL THIS DATA..
24. And finally, when you consider when you look at space from a clear sky in Montana, and can see the whole fuking Milky Way. WHY IS THERE NOT ONE GOD DAMN PHOTO FROM ORBIT OR ANY TIME NASA IS IN SPACE THAT SHOWS ANYTHING OTHER THAN A FEW TWINKLING STARS IN THE DISTANCE. And when there should be all that much more visible. More than ever possibly visible from Earth's surface... Must be a real collidescope... I COULD IMAGINE.....!

 

[Michael Scally MD]

[OA] Sex Hormone-Binding Globulin Regulation of Androgen Bioactivity In Vivo: Validation of The Free Hormone Hypothesis

Sex hormone-binding globulin (SHBG) is the high-affinity binding protein for androgens and estrogens.

According to the free hormone hypothesis, SHBG modulates the bioactivity of sex steroids by limiting their diffusion into target tissues.

Still, the in vivo physiological role of circulating SHBG remains unclear, especially since mice and rats lack circulating SHBG post-natally.

To test the free hormone hypothesis in vivo, we examined total and free sex steroid concentrations and bioactivity on target organs in mice expressing a human SHBG transgene.

SHBG increased total androgen and estrogen concentrations via hypothalamic-pituitary feedback regulation and prolonged ligand half-life.

Despite markedly raised total sex steroid concentrations, free testosterone was unaffected while sex steroid bioactivity on male and female reproductive organs was attenuated.

This occurred via a ligand-dependent, genotype-independent mechanism according to in vitro seminal vesicle organ cultures.

These results provide compelling support for the determination of free or bioavailable sex steroid concentrations in medicine, and clarify important comparative differences between translational mouse models and human endocrinology.

Laurent MR, Hammond GL, Blokland M, et al. Sex hormone-binding globulin regulation of androgen bioactivity in vivo: validation of the free hormone hypothesis. Sci Rep 2016;6:35539. Sex hormone-binding globulin regulation of androgen bioactivity in vivo: validation of the free hormone hypothesis : Scientific Reports