T3 may not be so good - increases SHBG

[Trevdog]

I think this deserves its own thread. Animal isn't Mr. Congeniality, but he has a brain.

Here is his post from his board"

"Now you see another reason why people are told to NOT take t3 with H or anything else. It increases SHBG! That being said, this little diddy also explains why somebody like me with low T levels and hypothyroid puts on muscle and/or retains it so well. BECAUSE MY SHBG IS LIKELY ALMOST ZERO!


Opposite effects of thyroid hormones on binding proteins for steroid hormones (sex hormone binding globulin and
corticosteroid binding globulin) in humans [published erratum appears in Eur J Endocrinol 1995 Sep;133(3):381
Author Dumoulin SC; Perret BP; Bennet AP; Caron PJ
Address
Department of Endocrinology' CHU Rangueil' Toulouse' France.
Source

Eur J Endocrinol, 132(5):594 8 1995 May
Abstract

Sex hormone binding globulin (SHBG) and corticosteroid binding globulin (CBG) levels were evaluated in euthyroid
(N = 111)' hyper (N = 58) and hypothyroid (N = 38) men' in pre and postmenopausal women (study 1) and in
hyper (N = 24) and hypothyroid (N = 15) patients before and after treatment with carbimazole or levothyroxine
therapy (study 2). The SHBG levels are increased in hyper and decreased in hypothyroid patients' whereas CBG
levels are increased in hypo and decreased in hyperthyroid patients. The SHBG levels are higher in women than in
men with similar thyroid status. Plasma SHBG levels are correlated positively whereas CBG levels are correlated
negatively with free thyroid hormone concentrations in men as well as women. In hypothyroid patients' SHBG
concentrations increased (p < 0.01) and CBG concentrations decreased (p < 0.01) during levothyroxine treatment. In
hyperthyroid patients' SHBG concentrations decreased (p < 0.01) and CBG concentrations increased (p < 0.01)

during antithyroid treatment. The SHBG and CBG concentrations in treated hypo and hyperthyroid patients were not
significantly different from those of euthyroid controls. Our data indicate that SHBG and CBG levels depend on thyroid
status. Corticosteroid binding globulin is an index of thyroid hormone action at the liver level whose changes are
opposite to those of SHBG in hyper and hypothyroidism.


And such, my little hobbits is EXACTLY why you lose muscle mass on T3. It IS NOT because of the t3 directly, but because it increases your shbg thereby locking up your testosterone and if you are dieting after a cycle with no AS at all, you can easily see how easy it would be to fuck yourself.

You been doing it WRONG for all these years and losing muscle because you were told BULLHSIT!"

 

[mvmaxx]

Interesting.

 

[fatchops]

I am confused

 

[Johny J]

shbg only binds to test correct? Well then i suppose while cutting i will drop test to 250mg and add in a bunch of other shit while taking t-3. It can bind away with the testosterone, because the other gear will be doing the work. Correct?

 

[xtinct]

The abstract is interesting but ultimately worthless because it doesn't tell us how much SHBG was elevated. If all it takes is another 100 or 200mg of test to compensate for increased SHBG then who cares?

 

[Drveejay11]

And such, my little hobbits is EXACTLY why you lose muscle mass on T3. It IS NOT because of the t3 directly, but because it increases your shbg thereby locking up your testosterone and if you are dieting after a cycle with no AS at all, you can easily see how easy it would be to fuck yourself.

...that's the most incorrect statement I have heard anyone try to SELL in a very long time. As intelligent as Animal IS (and he DOES posess a very advanced knowledge of AS), this statement scares me it's so OFF-BASE!!!!!

 

[Drveejay11]

J. Clin. Invest.
0021-9738/97/07/197/07 $2.00
Volume 100, Number 1, July 1997, 197-203

Inhibitors of the Proteasome Reduce the Accelerated Proteolysis in Atrophying Rat Skeletal Muscles
Nicholas E. Tawa Jr.*, Richard Odessey*, and Alfred L. Goldberg*

* Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115; and Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115

Several observations have suggested that the enhanced proteolysis and atrophy of skeletal muscle in various pathological states is due primarily to activation of the ubiquitin-proteasome pathway. To test this idea, we investigated whether peptide aldehyde inhibitors of the proteasome, N-acetyl-leucyl-leucyl-norleucinal (LLN), or the more potent CBZ-leucyl-leucyl-leucinal (MG132) suppressed proteolysis in incubated rat skeletal muscles. These agents (e.g., MG132 at 10 µM) inhibited nonlysosomal protein breakdown by up to 50% (P < 0.01), and this effect was rapidly reversed upon removal of the inhibitor. The peptide aldehydes did not alter protein synthesis or amino acid pools, but improved overall protein balance in the muscle. Upon treatment with MG132, ubiquitin-conjugated proteins accumulated in the muscle. The inhibition of muscle proteolysis correlated with efficacy against the proteasome, although these agents could also inhibit calpain-dependent proteolysis induced with Ca2+.

These inhibitors had much larger effects on proteolysis in atrophying muscles than in controls. In the denervated soleus undergoing atrophy, the increase in ATP-dependent proteolysis was reduced 70% by MG132 (P < 0.001). Similarly, the rise in muscle proteolysis induced by administering thyroid hormones was reduced 40-70% by the inhibitors. Finally, in rats made septic by cecal puncture, the increase in muscle proteolysis was completely blocked by MG132. Thus, the enhanced proteolysis in many catabolic states (including denervation, hyperthyroidism, and sepsis) is due to a proteasome-dependent pathway, and inhibition of proteasome function may be a useful approach to reduce muscle wasting. (J. Clin. Invest. 1997. 100:197-203.)

 

[Drveejay11]

J. Clin. Invest.
0021-9738/96/10/1703/06 $2.00
Volume 98, Number 8, October 1996, 1703-1708

RAPID PUBLICATION:
Muscle Wasting in Insulinopenic Rats Results from Activation of the ATP-dependent, Ubiquitin-Proteasome Proteolytic Pathway by a Mechanism Including Gene Transcription
S. Russ Price, James L. Bailey, Xiaonan Wang, Claudine Jurkovitz, Brian K. England, Xiaoyu Ding, Lawrence S. Phillips*, and William E. Mitch

Renal Division and * Division of Endocrinology and Metabolism, Emory University School of Medicine, Atlanta, Georgia 30322

In normal subjects and diabetic patients, insulin suppresses whole body proteolysis suggesting that the loss of lean body mass and muscle wasting in insulinopenia is related to increased muscle protein degradation. To document how insulinopenia affects organ weights and to identify the pathway for accelerated proteolysis in muscle, streptozotocin-treated and vehicle-injected, pair-fed control rats were studied. The weights of liver, adipose tissue, and muscle were decreased while muscle protein degradation was increased 75% by insulinopenia. This proteolytic response was not eliminated by blocking lysosomal function and calcium-dependent proteases at 7 or 3 d after streptozotocin. When ATP synthesis in muscle was inhibited, the rates of proteolysis were reduced to the same level in insulinopenic and control rats suggesting that the ATP-dependent, ubiquitin-proteasome pathway is activated. Additional evidence for activation of this pathway in muscle includes: (a) an inhibitor of proteasome activity eliminated the increased protein degradation; (b) mRNAs encoding ubiquitin and proteasome subunits were increased two- to threefold; and (c) there was increased transcription of the ubiquitin gene. We conclude that the mechanism for muscle protein wasting in insulinopenia includes activation of the ubiquitin-proteasome pathway with increased expression of the ubiquitin gene. (J. Clin. Invest. 1996. 98:1703-1708.)

 

[Drveejay11]

J Biol Chem, Vol. 273, Issue 39, 25216-25222, September 25, 1998


The N-end Rule Pathway Catalyzes a Major Fraction of the Protein Degradation in Skeletal Muscle
Vered Solomon, Stewart H. Lecker, and Alfred L. Goldberg
From the Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115

In skeletal muscle, overall protein degradation involves the ubiquitin-proteasome system. One property of a protein that leads to rapid ubiquitin-dependent degradation is the presence of a basic, acidic, or bulky hydrophobic residue at its N terminus. However, in normal cells, substrates for this N-end rule pathway, which involves ubiquitin carrier protein (E2) E214k and ubiquitin-protein ligase (E3) E3, have remained unclear. Surprisingly, in soluble extracts of rabbit muscle, we found that competitive inhibitors of E3 markedly inhibited the 125I-ubiquitin conjugation and ATP-dependent degradation of endogenous proteins. These inhibitors appear to selectively inhibit E3, since they blocked degradation of 125I-lysozyme, a model N-end rule substrate, but did not affect the degradation of proteins whose ubiquitination involved other E3s. The addition of several E2s or E3 to the muscle extracts stimulated overall proteolysis and ubiquitination, but only the stimulation by E3 or E214k was sensitive to these inhibitors. A similar general inhibition of ubiquitin conjugation to endogenous proteins was observed with a dominant negative inhibitor of E214k. Certain substrates of the N-end rule pathway are degraded after their tRNA-dependent arginylation. We found that adding RNase A to muscle extracts reduced the ATP-dependent proteolysis of endogenous proteins, and supplying tRNA partially restored this process. Finally, although in muscle extracts the N-end rule pathway catalyzes most ubiquitin conjugation, it makes only a minor contribution to overall protein ubiquitination in HeLa cell extracts.

 

[Greendragon]

ok lets just say what animal is saying has some truth to it. wouldn't a DHT based androgenic such as proviron remedy that situation by binding to SHBG.

just my .02

peace

green

 

[DTOX]

I'm not changing a goddamn thing.

1. He never said to what extent SHBG is altered, and what effect this has on Free Test levels.

2. Thyroid levels have a direct effect on not only protein metabolism but also insulin sensitivity.

 

[Trevdog]

Good points, all. I haven't deciphered the studies posted by Drveejay.

I really would rather not have to believe that T3 would increase SHBG substantially, but the study doesn't quantify it. I love T3.

I think it is true that only test binds to SHBG, but I don't remember. I bet hhadjo would know for sure. I'd like to see his comments on this anyway.

 

[Drveejay11]

I'm with ya Trev...let's BUMP for HAj........this is def in his arena. I PM'd him

 

[hhajdo]

T3 is catabolic because it activates ubiquitin-proteasome pathway of protein breakdown... Its effect on BV test doesn't contribute much to catabolism,IMO.
Your SHBG is low while on an Anabolic Androgenic Steroids (AAS) cycle because Anabolic Androgenic Steroids (AAS) lower it, adding T3 won't counteract the effect of Anabolic Androgenic Steroids (AAS) - it would be like worrying about the SHBG increase which occurs when a SERM like Tamoxifen or Clomid is administered....

And it takes little Anabolic Androgenic Steroids (AAS) to counteract T3 induced catabolism, in some studies I've seen they used about 10 mg of stanozolol or ox ED, or 200 mg of TE per week.

Also, the role of SHBG in human body is not fully understood. It regulates metabolic clearance rate of sex steroids, when SHBG decreases, the metabolic clearance rate increases - Nandi posted a study in which Proviron didn't cause an increase of free test because of this.
It can enhance (but also inhibit) the uptake of androgens, it can inhibit estradiol-induction of cell proliferation, etc...

 

[needsize]

very interesting thread

 

[Drveejay11]

T3 is catabolic because it activates ubiquitin-proteasome pathway of protein breakdown... Its effect on BV test doesn't contribute much to catabolism

 

[Trevdog]

Also, the role of SHBG in human body is not fully understood. It regulates metabolic clearance rate of sex steroids, when SHBG decreases, the metabolic clearance rate increases - Nandi posted a study in which Proviron didn't cause an increase of free test because of this.

Now I remember that post from Nandi. It may be that the level of SHBG in the body has little relevance because of the apparent inverse relationship between SHBG levels and clearance rate of steroids. The clearance rate and the SHBG level may in effect cancel each other out.

 

[Johny J]

I consulted with my testicles on this issue and they are writing up a formal thesis on their opinion. Will post when completed.

 

[Drveejay11]

Worthy of a BUMP