Results 1 to 11 of 11
  1. #1
    Elite knightmare999's Avatar
    Join Date
    Apr 2017
    Posts
    677
    Thanks
    644
    Thanked 514 Times in 317 Posts

    SHBG - Binding Affinities to Various Sex Hormones

    POB posted a link that really describes SHBG in depth:

    https://www.ncbi.nlm.nih.gov/pubmed/2080856

    Information below has been pulled from the above document.


    SHBG binds to testosterone, but it also bonds to other sex hormones (it was originally called "Testosterone-estradiol Binding Globulin). SHBG has an affinity for steroids (e.g., DHT, Testosterone, and e2).
    SHBG suppression relative to the presence of testosterone is called the Free Androgen Index.
    Calculating the Free Androgen Index can reveal hormonal anomalies that may escape detection via free testosterone measurement alone.

    For those that have only considered SHBG in relation to testosterone levels (as I originally did), observe the following:

    """
    Oestrogens administered orally are a more
    powerful stimulant of SHBG synthesis than
    those given percutaneously due to their direct
    absorption into the portal system. Antioestrogens such as clomiphene and tamoxifen" also induce SHBG synthesis presumably as a result of their inherent weak oestrogenic activity.
    Dexamethasone, progesterone and exogenous gonadotrophins have also been reported to increase SHBG concentration."""

    --------

    (The following is not from the document named above)

    Masteron, Winstrol, and other DHT derivatives are known for their ability to bind to SHBG and, reportedly, increase free testosterone. This effect presumably indicates that DHT has a higher binding preference to SHBG than test.
    What effects does this have on e2? Is DHT binding preferred above e2? Does increased free test also mean increased e2 (as e2 would also seemingly be unable to bind to SHBG already bound to Mast, etc.)

    Would love to hear other thoughts on SHBG or additional insight from those more knowledgeable than myself on the subject.



    Thanks.
    Nobody's neutral

  2. The Following User Says Thank You to knightmare999 For This Useful Post:

    Gazzamongo (05-18-2017)

  3. #2
    fitasfuk50's Operating System DocDePanda187123's Avatar
    Join Date
    Sep 2013
    Posts
    7,992
    Thanks
    1,514
    Thanked 5,428 Times in 3,158 Posts
    S I'm going to apologize in advance bc the information I've compiled is on two different things and I haven't taken the time to organize my thoughts so it's going to come out a little erratic.

    First, SHBG has a strong binding affinity to certain sex steroids. It binds to DHT>Test>Estrone/Estradiol. The Free Hormone Hypothesis is basically one that says only the free portion of the hormone is the active one. This hypothesis has come under heavy fire and basically been debunked. This is part of the reason ppl worry so much about free test but it's not the whole story.

    SHBG is made in the liver and it's basically a transport hormone for the most part. testosterone is fat soluble and not water soluble. Without SHBG, the testosterone made in your ballsack would not be able to enter into systemic circulation bc blood is mostly water. SHBG is a carrier protein that carries testosterone from your balls into your blood. SHBG is also like a time release function for testosterone bc testosterone metabolizes in the blood stream in 30-100min which would make T levels very low test bound to SHBG is not metabolized until it's free from the SHBG protein or the SHBG and its ligand (test) are bound to another receptor together. Albumin is the other major carrier protein and it has a weaker affinity for test than does SHBG. Affinity basically means how much effort is required to dissociate the bond once it's been made so the stronger the affinity the harder it is to separate the two molecules.

    There are also SHBG specific receptors in the body meaning that SHBG itself, or bound to test or another hormone, has specific physiologic purposes.

    My my main point here is to show that SHBG is not the enemy that many people make it out to be.

    Ill ll post a few things from Bill Roberts and Dr. Marianco next.
    II==[\\\\\\\\\\\\\\\]--------
    #Strength First Boston

  4. The Following 4 Users Say Thank You to DocDePanda187123 For This Useful Post:

    BRICKS (05-19-2017),knightmare999 (05-19-2017),Mythos (05-19-2017),widehips71 (05-19-2017)

  5. #3
    fitasfuk50's Operating System DocDePanda187123's Avatar
    Join Date
    Sep 2013
    Posts
    7,992
    Thanks
    1,514
    Thanked 5,428 Times in 3,158 Posts
    Dr. Crisler

    Let me explain some actual medicine to you. The concentration of androgens present during an AAS cycle so overuns the ability of SHBG to gobble them up that Free testosterone (or other androgens, as the case may be) is basically what you have in your bloodstream. SHBG levels simply do not and can not increase indefinitely.
    II==[\\\\\\\\\\\\\\\]--------
    #Strength First Boston

  6. The Following User Says Thank You to DocDePanda187123 For This Useful Post:

    Gazzamongo (05-19-2017)

  7. #4
    fitasfuk50's Operating System DocDePanda187123's Avatar
    Join Date
    Sep 2013
    Posts
    7,992
    Thanks
    1,514
    Thanked 5,428 Times in 3,158 Posts
    Bill Roberts




    On adding 100 mg/day oral Winstrol: You're likely to notice a substantial benefit.


    The benefits are from the Winstrol itself.


    I attribute none of the benefits to lowering SHBG.


    SHBG does not consume steroid or lower free levels.


    Many, including a number of medical professionals and even journal authors, in this case confuse the causation involved.


    Where total T levels are some given value, and SHBG is high, it will be found that free T levels are low.


    Mistakenly, one can assume that high SHBG is causing low free T, and come to a conclusion that lowering SHBG would improve free T. This theory gets treated as being a fact, even though no evidence is ever given of it working.


    But rather, free T is a given level, and high SHBG results in a higher total T value for that given level of free T. So the result is, low free T can be correlated with a midrange total T value. In this way, high SHBG level is correlated with "lower than expected" free T, on the assumption that total T is the factor directing homeostasis. (Which it isn't.)


    The answer isn't that SHBG is driving free T down, but rather that high SHBG is driving the total T value up.
    II==[\\\\\\\\\\\\\\\]--------
    #Strength First Boston

  8. #5
    fitasfuk50's Operating System DocDePanda187123's Avatar
    Join Date
    Sep 2013
    Posts
    7,992
    Thanks
    1,514
    Thanked 5,428 Times in 3,158 Posts
    Bill Roberts



    With regard to total T, the simplest thing is to not worry about this. But if one wants to, total T is the product, so to speak (not the exact result of arithmetic multiplication, but close) of free T concentration and SHBG concentration. So for same free T, more SHBG gives more total T, or less SHBG gives less total T. The driving force is those amounts, not the reverse: the free value is not derived from the total and the amount of SHBG, and nowhere in any receptor binding or enzyme kinetics equation will one find total T at all: only free.


    Any given estradiol molecule can interact with receptors any number of times. It is not consumed by that process.


    With regard to local metabolism of testosterone producing a locally higher level of estradiol, then that part of the body does have more estrogenic effect. This is diluted and averaged out as soon as that blood returns to the circulatory system.


    The difficulty with the middle-aged individual with low T is not that he has plenty of testosterone which his body is misapplying it. If he has low free T, he does not have plenty of testosterone. It is only confusing and deceptive to worry about "total T." The reason he has low free T, if he does, is low production. (In principle it could be unusually high metabolic elimination of testosterone, but I don't think this proves a major factor in practice. Higher estrogen levels are not indicative of this, as rather little T is lost from this pathway.)
    II==[\\\\\\\\\\\\\\\]--------
    #Strength First Boston

  9. #6
    fitasfuk50's Operating System DocDePanda187123's Avatar
    Join Date
    Sep 2013
    Posts
    7,992
    Thanks
    1,514
    Thanked 5,428 Times in 3,158 Posts
    Forgot who posted this



    Since the SHBG androgen sites are essentially SATURATED once endogenous TT reached 500 ng/dl, someone's SHBG value have LITTLE or NO INFLUENCE on exogenous AAS levels while cycling.


    So could/should a mates SHBG LEVEL alter the response to cycling?
    (such as warrant a change in dosing)


    NO!!


    Why? Because SHBG is essentially "SATURATED" while cycling.


    So the "extra AAS" has only THREE possible destinations once released from the parenteral DEPOT.


    Included are:


    1) intercellular/extracellular binding
    2) free "floating" within serum
    3) bound to ALBUMIN


    Because at TT levels of even 1000 ng/dl LESS THAN 1% of albumin sites are "occupied" the majority of that cycled anabolic will become BOUND TO ALBUMIN, (albumin can NOT saturate it's sites regardless of the "AAS level")
    II==[\\\\\\\\\\\\\\\]--------
    #Strength First Boston

  10. #7
    fitasfuk50's Operating System DocDePanda187123's Avatar
    Join Date
    Sep 2013
    Posts
    7,992
    Thanks
    1,514
    Thanked 5,428 Times in 3,158 Posts
    A PATIENT WITH ELEVATED testosterone AND GONADOTROPINS: IS IT SECONDARY HYPERGONADISM? [Abstract #1004] http://am.aace.com/sites/all/files/Abstract-Book.pdf


    Case Presentation: A 64- year old man was referred to Endocrinology section for evaluation of very high testosterone levels. Gonadal profile measured as the patient was complaining of fatigue and erectile dysfunction. Other Medical problems include chronic smoker, type 2 diabetes treated with insulin, chronic liver disease secondary to hepatitis C virus and depression.


    Physical exam showed normal testicular exam and no gynecomastia. Total testosterone level of more than 6000 ng/dl (241 - 827). Repeated blood work revealed a total testosterone of more than 1500 ng/dl free testosterone 16.65 ng/dl ( 5.0-21.0), beta-hcg <1 mIU/mL ( 0-3), alpha subunit 1.9 ng/mL ( < 0.6 ng/ml ), sex hormone binding globulin (SHBG) 158.3nm/l (19.3-76.4), LH 15.3 mIU/ml ( 1.2-10.8), FSH 9.5 mIU/ml ( 0.7-10.8), total estradiol 50.5 pg/ml (7.6- 42.6).


    Other results include, TSH 0.70 uIU/ml (0.4 - 4.0), albumin 3.6, alkaline phosphatase 79, AST 77 units/L (12 - 34), ALT 110 units/L (10 - 55). MRI of pituitary was done without any evidence of pituitary adenoma. Other pituitary and target function tests were normal.


    Repeat blood work up at 6 months revealed total testosterone 1045 ng/dl, free testosterone 10.5 ng/dl, SHBG 188.6 nm/l, LH 13 mIU/ml , FSH 9 mIU/ml , total estradiol 52.5 pg/ml, a free estradiol was came back 0.4 pg/ml ( 0.2-1.5 pg/ml).


    Discussion: The interesting features are: elevated LH level with high total testosterone and estradiol with normal free testosterone and low free estradiol level.


    This patient has elevated SHBG as a result of hepatitis C and chronic liver disease. SHBG bind both testosterone and estrogens. An elevated SHBG level explains the high total testosterone and high total estradiol. Gonadotropin levels are controlled via a negative feedback from free testosterone as well free estradiol. Estradiol exerts a strong negative feedback on the pituitary and decreases the release of gonadotropins. Therefore, in this patient, the elevated LH level can be attributed to either the low free estradiol level or to partial testosterone resistance.


    In view of elevated LH and elevated testosterone levels, other possibilities include gonadotroph adenomas and HCG secreting tumors. HCG levels being low, rules out HCG as the culprit. MRI pituitary has no evidence of pituitary adenoma.


    Conclusion: Patients with chronic liver disease may have elevated SHBG causing high total testosterone and estradiol. Free estradiol may become so low that it loses its ability to suppress gonadotropins. The resulting elevated gonadotropins and high total testosterone may mimic a picture of secondary hypergonadism. A partial testosterone resistance can’t be ruled out as well.
    II==[\\\\\\\\\\\\\\\]--------
    #Strength First Boston

  11. #8
    fitasfuk50's Operating System DocDePanda187123's Avatar
    Join Date
    Sep 2013
    Posts
    7,992
    Thanks
    1,514
    Thanked 5,428 Times in 3,158 Posts
    J Endocrinol Invest. 1984 Oct;7(5):489-94.
    Effect of D-thyroxine on serum sex hormone binding globulin (SHBG), testosterone, and pituitary-thyroid function in euthyroid subjects.
    Yosha S, Fay M, Longcope C, Braverman LE.
    Abstract
    Concentrations of serum sex hormone binding globulin (SHBG) and free testosterone (T) were examined in 10 euthyroid subjects (5 men and 5 women) before, during and after 30 days of the daily ingestion of 1 or 4 mg D-thyroxine (D-T4), the thyroxine analog that has only 1-15% of the calorigenic effect of L-thyroxine (L-T4). No changes in serum L-T4 or triiodothyronine (T3), serum cholesterol, SHBG, T, progesterone, estradiol-17 beta, or free T concentrations were observed in response to the 1 mg dose, but there was a slight elevation in the free thyroxine index (FTI) and a significant (p less than 0.02) suppression of the thyrotropin (TSH) response to thyrotropin releasing hormone (TRH). The 4 mg dose of D-T4 induced an increase in SHBG levels in all but one man. There was a significant negative correlation between the SHBG and percent free T (p less than 0.05) although the mass of free T did not change. As a group, the women responded with a greater increase in SHBG and decrease in percent free T than the men. Serum cholesterol decreased (p less than 0.01), all serum thyroid hormone values measured by RIA were increased (p less than 0.01), and the TSH response to TRH was completely suppressed. Despite these changes, the subjects remained clinically euthyroid. Concentrations of testosterone, progesterone and estradiol-17 beta remained unchanged. Serum luteinizing hormone (LH), which was evaluated in the men only, also did not change during the daily administration of 4 mg D-T4.
    PMID: 6542576 DOI: 10.1007/BF03348455
    II==[\\\\\\\\\\\\\\\]--------
    #Strength First Boston

  12. #9
    fitasfuk50's Operating System DocDePanda187123's Avatar
    Join Date
    Sep 2013
    Posts
    7,992
    Thanks
    1,514
    Thanked 5,428 Times in 3,158 Posts
    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
    II==[\\\\\\\\\\\\\\\]--------
    #Strength First Boston

  13. #10
    Elite knightmare999's Avatar
    Join Date
    Apr 2017
    Posts
    677
    Thanks
    644
    Thanked 514 Times in 317 Posts
    Lots of great info, Doc. Thanks for your time putting it together for us.

  14. #11
    fitasfuk50's Operating System DocDePanda187123's Avatar
    Join Date
    Sep 2013
    Posts
    7,992
    Thanks
    1,514
    Thanked 5,428 Times in 3,158 Posts
    More from Dr. Mariano




    "The lower the SHBG, the more likely testosterone level is going to be low since free testosterone has a half-life of only 10 to 100 minutes.

    Without SHBG, nearly all testosterone (unless it is continuously produced) would be gone from the body in less than about 50 minutes to 8 hours, being destroyed by degradative enzymes, such as by those in the liver.

    The higher the SHBG, the lower the dose of testosterone is needed in treatment."
    II==[\\\\\\\\\\\\\\\]--------
    #Strength First Boston

Similar Threads

  1. Basic Application of Various Gear (How to setup your 2nd cycle)
    By TheLupinator in forum Anabolic Steroids
    Replies: 16
    Last Post: 12-11-2015, 05:54 PM
  2. need SHBG help
    By juuced in forum Testosterone and Hormone Replacement Therapy
    Replies: 9
    Last Post: 01-22-2013, 05:26 PM
  3. SHBG not tested by doctor? Important?
    By eatspinach in forum Testosterone and Hormone Replacement Therapy
    Replies: 5
    Last Post: 10-20-2012, 08:00 AM

Tags for this Thread

Posting Permissions

  • You may not post new threads
  • You may not post replies
  • You may not post attachments
  • You may not edit your posts
  •