What/how do steroids have an affinity to SHBG ?

[guest589745]

How do you determine which steroids have an affinity to SHBG ?

How do you determine how much a steroid effects SHBG ? Can you ?

First person to make a list with this info is a badass mother****er

[BajanBastard]

You'll need to read up on studies which tested the RBA of certain steroids for SHBG. Steroids with a low RBA for the AR in muscle may have a higher RBA for SHBG.

[guest589745]

The RBA is what baj ? Receptor Binding Affinity ?

[guest589745]

i got this so far but I need to read it again, and again after that probly lol.

* Saartok T,
* Dahlberg E,
* Gustafsson JA.

It is unclear whether anabolic steroids act on skeletal muscle via the androgen receptor (AR) in this tissue, or whether there is a separate anabolic receptor. When several anabolic steroids were tested as competitors for the binding of [3H]methyltrienolone (MT; 17 beta-hydroxy-17 alpha-methyl-4,9,11-estratrien-3-one) to the AR in rat and rabbit skeletal muscle and rat prostate, respectively, MT itself was the most efficient competitor. 1 alpha-Methyl-5 alpha-dihydrotestosterone (1 alpha-methyl-DHT; mesterolone) bound most avidly to sex hormone-binding globulin (SHBG) [relative binding affinity (RBA) about 4 times that of DHT]. Some anabolic-androgenic steroids bound strongly to the AR in skeletal muscle and prostate [ RBAs relative to that of MT: MT greater than 19-nortestosterone ( NorT ; nandrolone ) greater than methenolone (17 beta-hydroxy-1-methyl-5 alpha-androst-1-en-3-one) greater than testosterone (T) greater than 1 alpha-methyl-DHT]. In other cases, AR binding was weak (RBA values less than 0.05): stanozolol (17 alpha-methyl-5 alpha- androstano [3,2-c]pyrazol-17 beta-ol), methanedienone (17 beta-hydroxy-17 alpha-methyl-1,4-androstadien-3-one), and fluoxymesterolone (9 alpha-fluoro-11 beta-hydroxy-17 alpha-methyl-T). Other compounds had RBAs too low to be determined (e.g. oxymetholone (17 beta-hydroxy-2-hydroxymethylene-17 alpha-methyl-5 alpha-androstan-3-one) and ethylestrenol (17 alpha-ethyl-4- estren -17 beta-ol). The competition pattern was similar in muscle and prostate, except for a higher RBA of DHT in the prostate. The low RBA of DHT in muscle was probably due to the previously reported rapid reduction of its 3-keto function to metabolites, which did not bind to the AR [5 alpha-androstane-3 alpha, 17 beta-diol and its 3 beta-isomer (3 alpha- and 3 beta-adiol, respectively)]. Some anabolic-androgenic steroids (only a few synthetic) bound to SHBG (1 alpha-methyl-DHT much greater than DHT greater than T greater than 3 beta-adiol greater than 3 alpha-adiol = 17 alpha-methyl-T greater than methenolone greater than methanedienone greater than stanozolol). The ratio of the RBA in rat muscle to that in the prostate (an estimate of the myotrophic potency of the compounds) was close to unity, varying only between about 0.4 and 1.7 in most cases.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID: 6539197 [PubMed - indexed for MEDLINE]

[guest589745]

Not many options when it comes to trying to lower SHBG levels
Supplements that lower SHBG:
-Proviron
-GH
-Avena Sativa Extract/Green oat that contains Avenacosidas-supposedly there is none of this product out on the market that shows that it works.
-Carao Extract-Theory only-has not been proven yet
-Utica Dioca aka Stinging Nettles
-Muira Puama

Clomid and Nolvadex increas SHBG levels.

???

[guest589745]

• Under-eating is related to higher SHBG concentrations.

• Over-training is related too.

• Over-eating, conversely, lowers SHBG.

• Insulin is inversely related to SHBG levels.

• Particular supplements appear to reduce SHBG binding.

In a nutshell, consuming two to three protein-carb meals before lunch and two protein-fat meals after lunch seems a decent "androgen emancipation" strategy. It should keep insulin levels reasonably high while providing both proper substrates to muscle and reducing SHBG. The probable free-Testosterone elevation over time should help the higher circulating insulin that you're cultivating do it's anabolic / anti-catabolic thing. And let's not forget, early or late, workouts generally enable an additional carb meal post-exercise, so take advantage of them. Getting an insulin spike when Testosterone and GH are also high is like hiring three construction workers at once!

Okay, now that we know how to carefully jack-up insulin regularly enough to keep SHBG from hog tying our precious T, let's briefly talk supplements. Perhaps the most interesting is Avena sativa, or green oat, like that found in Biotest's Tribex-500. Data on this stuff are sparse but there is some suggestion that it combats SHBG. An often touted but unpublished report from the Institute for Advanced Study of Human Sexuality in San Francisco suggests that green-oat extracts do release Testosterone from its binding proteins.

And as a side note, Japanese research suggests increased luteinizing hormone (LH) secretion as well, via interactions with the anterior pituitary gland itself (6, 9). Yeah, these latter studies were done in amenorrheic women, but I told you the data were sparse! Anyhow, the combined effect could well be higher circulating concentrations of free T, even in men.

The other general approach is to simultaneously raise total T and free-T via prohormones. Although unpublished, I've seen first hand that androstenediol, for example, can raise serum Testosterone levels with the bound (SHBG-tied) and unbound levels rising simultaneously. One could very well speculate that a prohormone (or other steroid ), combined with green oat supplementation and natural (or unnatural) insulin elevation could be quite the ticket for muscle anabolism.

To summarize our "unleashing" plan, we need to 1) Eat every 2-3 hours, focusing on protein with carbs in the morning and protein with "healthier fats" in the evening 2) Allow for adequate rest — perhaps two "off" days weekly — to prevent over-training 3) Limit high-volume training cycles to just a few weeks, and 4) Possibly consider a 2-4 week course of Avena sativa along with the frequent eating to see if one's prohormones, (etc.) are more effective.

With the person-to-person variation in SHBG being on the order of 40-50% (27), these "unleashing" suggestions may be just the ticket for those of you who have high SHBG and don't even know it. Although the "free hormone hypothesis" debate rages on, it is an interesting scenario — especially if we can control it. If you get less progress from a cycle of androgens than your gloating training buddy, SHBG may be involved. Perhaps the data mentioned here is your missing factor. In any case, the research suggests a new mechanism for the wonders of massive, disciplined eating.

Sex hormone-binding globulin (SHBG) is a glycoprotein synthesized by the liver. Circulating androgen and estrogen concentrations influence SHBG synthesis. The regulation of SHBG synthesis, combined with SHBG's higher affinity for testosterone, impacts bioavailable testosterone levels.

SHBG binds up to 98 percent of the steroid hormones in the blood including 5a-dihydrotestosterone (DHT), testosterone and androstenediol with particularly high affinity, and estradiol and estrone with slightly lower affinity

Male and female children have similar SHBG concentrations until the onset of puberty, when SHBG levels begin decreasing more rapidly in males than in females. Levels are higher in women than in men, due to the higher ratio of estrogens to androgens in women. Levels are especially elevated during late pregnancy and in women taking oral contraceptives.

True androgen status can be assessed either by measuring free testosterone or by calculating the ratio of total testosterone to SHBG, known as the free androgen index (FAI).

Conditions that suggest Low SHBG:
Hormones Hirsutism Because SHBG is often low in women with hirsutism, free testosterone is elevated while the total testosterone concentration is normal. This means the free testosterone portion is responsible for increased male characteristics. Just an increase in free testosterone with no increase in total testosterone can produce significant consequences.

Hypothyroidism Modest reductions in SHBG levels may be encountered in individuals with hypothyroidism.

Hyperprolactinemia Modest reductions in SHBG levels may be encountered in individuals with hyperprolactinemia.

Lab Values
Elevated Cortisol Levels Modest reductions in SHBG levels may be encountered in individuals with Cushing's syndrome.

Metabolic
Problems Caused By Being Overweight SHBG levels respond to extreme changes in body weight, decreasing in obese patients.

Skin-Hair-Nails
Adult Acne Low levels are often found in cases of acne vulgaris.

Uro-Genital
Polycystic Ovary Syndrome (PCOS) Low levels are often found in cases of polycystic ovary syndrome. SHBG is low in about 50% of cases.

Risk factors for Low SHBG:
Drug Side Effects Prescription Drug Side-Effects Modest reductions in SHBG levels may be encountered in individuals receiving glucocorticoids such as prednisone.


Environment / Toxicity
General Detoxification Requirement Aromatase is the enzyme that converts androgen to estrogen. Aromatase is an important target of some environmental chemicals. Some of these compounds inhibit aromatase activity, resulting in a decrease in the level of estrogen or an increase in the level of androgen in cells. Environmental chemicals can also modify the expression of aromatase in various tissues, resulting in a change in the ratio between androgen to estrogen. The compounds that inhibit aromatase or suppress aromatase expression will behave as antiestrogens or androgen-like compounds in vivo. On the other hand, compounds that increase aromatase expression or enhance aromatase activity (or stability) may function as anti-androgens or estrogen-like compounds.

Hormones
High Testosterone Level, Male
High Testosterone Level, Female Elevated testosterone causes SHBG synthesis to decrease, lowering its level in the blood.

Low Progesterone or Estrogen Dominance Elevated estrogen levels stimulate SHBG production, increasing levels in the blood.


Lab Values - Hormones
Very/moderately low SHBG

Counter-indicators:
Elevated SHBG

Laboratory Test Needed
Elevated Insulin Levels Research has discovered that sex hormone binding globulin (SHBG), a relatively unknown blood protein, is a reasonably good indicator of insulin resistance. Low levels of SHBG are consistently linked to high levels of insulin in the body. Sustained high levels of insulin are, in turn, associated with the development of the chronic diseases such as high blood pressure, diabetes and coronary heart disease.

Low SHBG suggests the following may be present:
Drug Side Effects Prescription Drug Side-Effects Modest reductions in SHBG levels may be encountered in individuals receiving glucocorticoids such as prednisone.

Recommendations for Low SHBG:
Diet Weight Loss As weight loss will improve insulin resistance, and insulin resistance can be measured by low SHBG, weight loss should help normalize low SHBG levels.

Gluten-free Diet Substituting rice for wheat, which generally has a lower amylase content, can raise SHBG levels via lowered insulin levels. However, starches should be restricted when trying to lower insulin levels.

Drug
Conventional Drugs Selection of an OC formulation that maintains increases in SHBG may be important in minimizing androgenic effects in general, and especially important in hyperandrogenic women, who may benefit most from reductions in levels of free testosterone.

SHBG's may be lowered by two of the artificially generated progesterones, norgestrel and norethisterone. If you are a woman who may be susceptible to androgenetic alopecia, that is, hereditary hair loss (female pattern baldness), or you have a naturally low SHBG level, you should avoid any contraceptive pills or hormone replacement therapy that contains synthetic progesterone.

Extract
Not recommended:
DIM (di-indolmethane)/I3C (Indole-3-Carbinol) Aromatase inhibitors like DIM, Indole 3 carbinol, and chrysin should be avoided, as they will enhance any preexisting androgen / estrogen dominance.

Hormone
Estrogen Replacement The use of estrogen to increase SHBG and hence reduce biologically free testosterone may lessen acne and hirsutism. This mechanism is commonly operative in women with Polycystic Ovarian Syndrome. With estrogen replacement, estrogen levels are higher and liver production of SHBG increases. With pregnancy or some birth control pills, you will have high SHBG, and you will have high levels of circulating hormones, but they will be mostly bound (including testosterone).

Although this article was primarily written for women, all the info is also applicable to men.

How winny and proviron will make your cycle kick ass
Really, only a very small amount of Testosterone exists as “free” testosterone. Free test is testosterone that capable of binding to the Androgen Receptor, which is where all the rest of the magic happens, and allows for the following benefits:
-Enhanced growth factor activity (e.g. GH, IGF-1, etc.)
-Enhanced activation of myogenic stem cells (i.e. satellite cells)
-Enhanced myonuclear number (to maintain nuclear to cytoplasmic ratio)
-Enhanced protein synthesis
-New myofiber formation

Testosterone binds at around 45% to what is known as Sex Hormone Binding Globulin (SHBG), and about another 53% binds to proteins (albumin). The rest exists in a “free” state (about 2% if you did your math). Different variations of steroids also differ in the way in which they bind to proteins.
If one could unbind testosterone from SHBG by even a small percentage, it could make a big difference in the way that testosterone or other AAS exert their anabolic effects. Studies show that when testosterone is unbound from SHBG the “free” test does in fact exert greater effects than total T. As the following studies support:
-
Demisch K, and Nickelsen T. Distribution of testosterone in plasma proteins during replacement therapy with testosterone enanthate in patients suffering from hypogonadism Andrologia 1983;15 Spec No:536-41.

Gandar R. Interpretation of the blood level of a steroid Rev Fr Gynecol Obstet 1985 Aug-Sep;80(8-9):635-40.

Legrand E., et al. Osteoporosis in men: a potential role for the sex hormone binding globulin Bone 2001 Jul;29(1):90-5.

Longcope C., et al. Diet and sex hormone-binding globulin. J Clin Endocrinol Metab 2000 Jan;85(1):293-296.

Valero-Politi J, and Fuentes-Arderiu X. Within- and between-subject biological variations of follitropin, lutropin, testosterone, and sex-hormone-binding globulin in men. Clin Chem 1993 Aug;39(8):1723-1725.

Proviron(1-Methyl Dihydrotestosterone) has been shown to bind with SHBG much more readily than test.



Relative binding affinity of anabolic-androgenic steroids: comparison of the binding to the androgen receptors in skeletal muscle and in prostate, as well as to sex hormone-binding globulin.

Saartok T, Dahlberg E, Gustafsson JA.

It is unclear whether anabolic steroids act on skeletal muscle via the androgen receptor (AR) in this tissue, or whether there is a separate anabolic receptor. When several anabolic steroids were tested as competitors for the binding of [3H]methyltrienolone (MT; 17 beta-hydroxy-17 alpha-methyl-4,9,11-estratrien-3-one) to the AR in rat and rabbit skeletal muscle and rat prostate, respectively, MT itself was the most efficient competitor. 1 alpha-Methyl-5 alpha-dihydrotestosterone (1 alpha-methyl-DHT; mesterolone) bound most avidly to sex hormone-binding globulin (SHBG) [relative binding affinity (RBA) about 4 times that of DHT]. Some anabolic-androgenic steroids bound strongly to the AR in skeletal muscle and prostate [ RBAs relative to that of MT: MT greater than 19-nortestosterone ( NorT ; nandrolone ) greater than methenolone (17 beta-hydroxy-1-methyl-5 alpha-androst-1-en-3-one) greater than testosterone (T) greater than 1 alpha-methyl-DHT]. In other cases, AR binding was weak (RBA values less than 0.05): stanozolol (17 alpha-methyl-5 alpha- androstano [3,2-c]pyrazol-17 beta-ol), methanedienone (17 beta-hydroxy-17 alpha-methyl-1,4-androstadien-3-one), and fluoxymesterolone (9 alpha-fluoro-11 beta-hydroxy-17 alpha-methyl-T). Other compounds had RBAs too low to be determined (e.g. oxymetholone (17 beta-hydroxy-2-hydroxymethylene-17 alpha-methyl-5 alpha-androstan-3-one) and ethylestrenol (17 alpha-ethyl-4- estren -17 beta-ol). The competition pattern was similar in muscle and prostate, except for a higher RBA of DHT in the prostate. The low RBA of DHT in muscle was probably due to the previously reported rapid reduction of its 3-keto function to metabolites, which did not bind to the AR [5 alpha-androstane-3 alpha, 17 beta-diol and its 3 beta-isomer (3 alpha- and 3 beta-adiol, respectively)]. Some anabolic-androgenic steroids (only a few synthetic) bound to SHBG (1 alpha-methyl-DHT much greater than DHT greater than T greater than 3 beta-adiol greater than 3 alpha-adiol = 17 alpha-methyl-T greater than methenolone greater than methanedienone greater than stanozolol). The ratio of the RBA in rat muscle to that in the prostate (an estimate of the myotrophic potency of the compounds) was close to unity, varying only between about 0.4 and 1.7 in most cases.(ABSTRACT TRUNCATED AT 400 WORDS)


Skalba P, Korfanty A, Mroczka W, Wojtowicz M. Related Articles
[Changes of SHBG concentrations in postmenopausal women]
Ginekol Pol. 2001 Dec;72(12A):1388-92. Polish.


Variations of sex hormone-binding globulin in thyroid dysfunction.

Brenta G, Schnitman M, Gurfinkiel M, Damilano S, Pierini A, Sinay I, Pisarev MA.

Department of Endocrinology and Metabolism, French Hospital, Buenos Aires, Argentina. [email protected]

With the aim of understanding the variations of the levels of sex hormone-binding globulin (SHBG) in thyroid dysfunction, we studied the influence of factors that also modify SHBG, such as menopausal status, age, and body mass index (BMI) in women with hypothyroidism and hyperthyroidism, both overt and subclinical. Statistical analysis was performed by means of analysis of variance (ANOVA), stepwise multiple regression, and partial correlation. The ANOVA showed a significant statistical difference among the means of SHBG of all groups (p<0.01). The difference was due to the group that included hyperthyroid women. Multiple regression analysis showed that the main factors influencing SHBG were BMI and age, except for the hyperthyroid group, where the most important independent variables were triiodothyronine (T3) and thyroxine (T4). Partial correlation controlling the effect of BMI and age showed no association between SHBG and the other variables in all groups except for the subclinical hyperthyroid and hyperthyroid, where we found a significant association between SHBG and T4 and T3. The premenopausal or postmenopausal status did not modify SHBG levels. When the patients are taken as a whole, BMI, age, T4, and T3 all have an association with SHBG levels according to the multiple regression analysis.

Determinants of sex hormone-binding globulin blood concentrations in premenopausal and postmenopausal women with different estrogen status. Virgilio-Menopause-Health Group.

Pasquali R, Vicennati V, Bertazzo D, Casimirri F, Pascal G, Tortelli O, Labate AM.

Department of Internal Medicine and Gastroenterology, University of Bologna, Italy

Just a quote: 2) SHBG values are correlated positively with estradiol and negatively with insulin and testosterone concentrations, but the predictive value of these variabiles on SHBG appears to be different in premenopause and postmenopause;

Here is a fun little fact: the level of SHBG can also be influenced by other factors. There is a direct relationship between the level of estrogen and thyroid hormones and the level of SHBG. Estrogen goes up, SHBG goes up. Estrogen goes down SHBG goes down. Same for Thyroid hormones triiodothyronine (T3) and thyroxine (T4). Also, there is a relationship with diet and insulin, but that is something I will save for later. Higher androgen levels due to AS administration has been shown to considerably lower levels of SHBG as well. The AS Winstrol (stanozolol) was shown in a 1989 study to lower levels of SHBG by 50% after oral administration.




Sex hormone-binding globulin response to the anabolic steroid stanozolol: evidence for its suitability as a biological androgen sensitivity test.

Sinnecker G, Kohler S.

Department of Pediatrics, University of Hamburg, West Germany.

Both the androgen-induced decline in serum sex hormone-binding globulin (SHBG) levels during puberty and the anabolic effect of exogenous testosterone are absent in patients with androgen insensitivity (testicular feminization). To determine whether the androgen-induced decline in serum SHBG could be used as a test of androgen sensitivity, we studied the effect of the anabolic-androgenic steroid stanozolol (17 beta-hydroxy-17 alpha-methyl-5 alpha-androstano-[3,2-c]pyrazol) on serum SHBG in 25 control subjects, 3 patients with complete androgen insensitivity, and 4 patients with partial androgen insensitivity. Stanozolol was administered orally for 3 days (0.2 mg/kg.day); blood samples were taken before and 5, 6, 7, and 8 days after the beginning of the test for measurements of serum SHBG. The lowest value (i.e. the peak response) in each subject was used as the measure of the response to stanozolol. In the control subjects the mean nadir serum SHBG level was 51.6 +/- 5.9% (+/- SD) of the initial value (P less than 0.001). In the 4 patients with partial androgen insensitivity the nadir serum SHBG ranged from 73-89%, and in the 3 patients with complete androgen insensitivity it ranged from 93-97% of the initial value. Thus, the decrease in serum SHBG after short term administration of stanozolol reflects androgen responsiveness and, thus, may be used to differentiate patients with androgen insensitivity syndromes from those with other causes of male pseudohermaphroditism.

Here’s the thing: This was after oral administration, so I am not sure that I can extrapolate the data to injectable as well. SHBG is made in the liver so even an injectable winny would have to be processed there, albeit slower, due to the slower release of injectable winny and it’s direct release into the bloodstream. That could possibly make it a little less effective in this regard.

[guest589745]

For you captain

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Thanks Skull