any info on "clear"

[akinbacon]

I keep reading articles on this balco thing. They keep refering to "designer" steroid, and the name they gave it is the "clear" Does anyone have any info on it?

 

[rAJJIN]

Yea the clear and the cream.
I never realy understood exactly what it was either.
Some kind Of designer steroid that was suppose to be undedetectable I thought. Good question though...Im curious exactly what it was as well.

 

[K1]

Yea the clear and the cream.
I never realy understood exactly what it was either.
Some kind Of designer steroid that was suppose to be undedetectable I thought. Good question though...Im curious exactly what it was as well.

Isn't that the shit that they say Bond's was taking, the clear and the cream??!

 

[sammarbella]

This is old man.

Even wikipedia knows it.

I love google and i know how to use it:

http://en.wikipedia.org/wiki/Tetrahydrogestrinone

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Tetrahydrogestrinone

Tetrahydrogestrinone (often referred to as THG or "the clear") is an anabolic steroid. It has affinity to the androgen receptor and the progesterone receptor, but not to the estrogen receptor.[1] The drug has been considered a "designer drug", closely related to the banned anabolic steroids gestrinone and trenbolone,[2] and was banned by the Food and Drug Administration (FDA) at the end of 2003.[3]

It was created by an American chemist named Patrick Arnold, who is also supposed to be the father of pro-hormones in nutritional supplements market of the United States.[citation needed]

Anecdotal sources and some unpublished SAR studies report that the potency of the drug is outstanding, surpassing, on a milligram per milligram basis, every known synthesized or commercial available anabolic steroid. It was the drug of choice for safe and "invisible" world record breaking in athletics.[citation needed]

The drug was again made public when the United States Anti-Doping Agency was contacted by an anonymous athletics coach, later identified as Trevor Graham who claimed that several top athletes were using THG and provided the USADA with a syringe containing THG, which the USADA then used to develop a test for the substance.[4]

The USADA identified the Bay Area Laboratory Co-operative (BALCO), an American nutritional supplement company, as the source of THG.[citation needed] The company manufactured the drug through palladium-charcoal catalyzed hydrogenation from gestrinone, a substance used in gynecology for treatment of endometriosis.[citation needed]

THG had been distributed to several leading athletes, including many during the BALCO scandal.

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[rAJJIN]

so it sounds Like it was simm to tren.
I wasnt sure exactly what it was... Something Pat Arnold made though huh...
Crazy, small world I guess.

 

[sammarbella]

so it sounds Like it was simm to tren.
I wasnt sure exactly what it was... Something Pat Arnold made though huh...
Crazy, small world I guess.

Hummm, at first sight reading the previous maybe but look at the following study.

It has DHT affinities and nandrolone/progestin (trenbolone) similarities.

An unique and strange beast.:twisted:

I think is the only avalaible study.(the others seems unpublished)

http://endo.endojournals.org/cgi/rapidpdf/en.2005-0448v1.pdf

(Extracted)

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Endocrinology. First published June 23, 2005 as doi:10.1210/en.2005-0448

Tetrahydrogestrinone is an Androgenic Steroid That Stimulates Androgen
Receptor-Mediated, Myogenic Differentiation in C3H10T1/2 Multipotent
Mesenchymal cells and Promotes Muscle Accretion in Orchidectomized, Male Rats

R. Jasuja1,3*, D. H. Catlin2, A. Miller3, Y.-C. Chang2, K. L. Herbst1,3, B. Starcevic2, J. N.
Artaza1,3, R. Singh3, G. Datta1, A. Sarkissian1, C. Chandsawangbhuwana 4, M. Baker4, and S.
Bhasin1,3.
1Section of Endocrinology, Boston University, Boston, MA
2Department of Molecular and Medical Pharmacology, University of California, Los Angeles
3Division of Endocrinology, Charles R. Drew University of Medicine, Los Angeles
4Department of Medicine, University of California, San Diego
Address for correspondence and reprints:

Ravi Jasuja, Ph.D.
Boston University Medical Center
Boston University
E201, 88 E. Newton Street
Boston, MA 02117
Phone: 617 414 1833
Email: [email protected]

Grant Support: This study was supported by grants 3S06-GM068510-02S1 (R.J.),
1RO1HD043348, 1RO1DK 070534, U54HD041748, RCMI grants P20RR11145, G12RR03026,
and UARP Drew Cares HIV Center grant.

Copyright (C) 2005 by The Endocrine Society

ABSTRACT

The discovery of tetrahydrogestrinone (THG) abuse by several elite athletes led the US
Congress to declare it a controlled substance, although conclusive evidence of its
anabolic/androgenic activity is lacking. We determined whether THG affects myogenic
differentiation and androgen receptor (AR)-mediated signaling, binds to AR, and whether it has
androgenic and anabolic effects in vivo. Accordingly, we measured the dissociation constant for
THG with a fluorescence anisotropy assay using recombinant AR-ligand binding domain (LBD).
The AR nuclear translocation and myogenic activity of androstenedione were evaluated in
mesenchymal, multipotent C3H10T1/2 cells. We performed molecular modeling of the THG:AR
interaction. The androgenic/anabolic activity was evaluated in orchidectomized rats.

THG bound to AR with an affinity similar to that of DHT. In multipotent C3H10T1/2
cells, THG upregulated AR expression, induced AR nuclear translocation, dose-dependently
increased the area of myosin heavy chain type II (MHC-II) positive myotubes, and upregulated
MyoD and MHC-II protein expression. The interaction between AR and the A ring of THG was
similar to that between AR and the A ring of DHT, but the C17 and C18 substituents in THG had
a unique stabilizing interaction with AR. THG administration prevented the castration-induced
atrophy of levator ani, prostate gland, and seminal vesicles, and loss of fat-free mass in
orchidectomized rats. We conclude that THG is an anabolic steroid that binds to AR, activates
AR-mediated signaling, promotes myogenesis in mesenchymal multipotent cells and has
anabolic and androgenic activity in vivo. This mechanism-based approach should be useful for
rapid screening of anabolic/androgenic agents.
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RESULTS

THG Binds Ligand Binding Domain of AR with an Affinity Similar to that of DHT

We evaluated the affinity of THG for the AR using a fluorescence polarization assay [17,
24] in which the displacement of a fluorescent androgen (FA) analog from the purified AR-LBD
by THG was determined. The relative binding affinities for THG, 4-androstendione, and DHT
were 8.4 ± 1.2, 646±22, and 9.8 ± 1.4 nM, respectively (Figure 1A).

A Molecular Model of THG:AR Interaction (Figure 1B)

The finding that THG has either equal or slightly higher affinity for AR than DHT was
unexpected because THG contains substituents at C17 and C18 that could potentially have
unfavorable steric interactions. To identify the amino acid residues that interact with THG, we
constructed a 3D-structural model of AR interaction with THG. Interestingly, the D ring, an
important determinant of steroid specificity [25-29] displays unique stabilizing interactions with
AR. THG has an extra methyl group at C18 and a 17a-ethyl substituent that are lacking in DHT,
testosterone, or R1881. The 3D model shows that the LBD of AR accommodates the 17a-ethyl
substituent with stabilizing van der Waals interactions between THG and AR. Cß on Leu-701
and Leu-704 are 3.95A and 3.6A, respectively from THG, and Cd2 on Leu-880 is 3.45A from
THG (Figure 1B). Moreover, two of these leucine residues have stabilizing interactions with
each other. Thus, Cd2 on Leu880 is 3.7A from Cd2 of Leu-701.

The 3D model also shows that the C18 substituent on THG has a unique stabilizing
interaction with Trp-741, which has rotated from its orientation in the AR-DHT complex, in
which it interacts with the C19 methyl group. In the AR-THG complex, C.2 on Trp-741 is 4A
from THG. Moreover, Met-895 Sd is closer to Trp-741 and Ce on Met-895 is 4A from THG,
which is 3.55A from O. on Thr 877.


THG Induces Nuclear Translocation of AR

The initial step in AR signaling is ligand-induced nuclear translocation of the receptor [715,
19]. To determine if THG-bound receptor acquires the transcriptionally active conformation
to translocate into the nucleus, multipotent C3H10T1/2 cells were treated with graded THG
doses in sub-confluent cultures. The spatial distribution of AR was determined by using
immunocytochemical staining (Figure 2). AR staining was mostly cytoplasmic in control wells
treated with medium alone; co-incubation with THG or DHT caused AR to translocate into the
nucleus (Figure 2). THG-induced AR nuclear translocation was attenuated by co-incubation with
a 10-fold excess of an AR antagonist, bicalutamide, indicating that this was an AR-mediated
process and also providing evidence of the specificity of this effect.

THG Promotes Myogenic Differentiation of Mesenchymal, Multipotent, C3H10T1/2 Cells

We have shown previously that C3H10T1/2 cells express AR protein and that androgens
induce the expression of AR in these cells [10]. Incubation with graded concentrations of THG
unregulated AR dose-dependently.

C3H10T1/2 cells have been used widely as a model to investigate modulation of lineage
determination [30-32]. Androgens, such as testosterone, DHT, and 4-androstenedione cause
preferential commitment and differentiation of C3H10T1/2 multipotent cells into myogenic
lineage and up regulate the transcriptional markers in myogenic differentiation [10,17].
Incubation of C3H10T1/2 cells with graded THG concentrations (1-30 nM) led to a dose-
dependent increase in myosin heavy chain II-positive (MHC+) myotubes, quantified using image
analysis (Figure 3B).

THG up regulated dose-dependently MyoD and MHC-II protein expression (Figure 3A).
The effects of 30 nM THG were not significantly different from those of 30 nM DHT. Thus,

THG promotes the differentiation of mesenchymal, multipotent cells in to the myogenic lineage
with potency not dissimilar from DHT.

THG has Anabolic and Androgenic Activity in vivo in the Castrated Male Rat Model

We evaluated the androgenic and anabolic activity of THG in a castrated rat model, using
levator ani muscle mass and whole body fat-free mass (FFM) measured by DEXA as markers
for anabolic activity, and prostate and seminal vesicle weights as markers for androgenic activity.
Orchidectomized rats had significantly lower FFM (p<0.05) than sham-operated controls (Figure
4A). The FFM of orchidectomized rats treated with either 75 or 150 ug dose of THG or
testosterone enanthate did not differ significantly from that of sham-operated controls, but was
significantly greater than that of orchidectomized, placebo-treated rats (Figure 4A).

Orchidectomized rats had significantly lower levator ani, prostate and seminal vesicle
weights compared to sham-operated controls; supplementation with THG or TE restored the
levator ani, prostate and seminal vesicle weights to levels observed in eugonadal controls. The
levator ani, prostate and seminal vesicle weights were significantly higher in THG and TE-
supplemented groups in comparison to castrated controls (Figure 4A and 4B).

DISCUSSION

THG, a derivative of gestrinone, possesses structural and functional similarities with
potent androgens. THG associates with the LBD of AR with an affinity similar to that of DHT
[33,35], induces AR-nuclear translocation, and promotes myogenic differentiation of
mesenchymal multipotent cells. THG mediated nuclear translocation of AR is attenuated by
bicalutamide, an AR-antagonist, suggesting that THG specifically competes for the AR binding
pocket occupancy. THG exerts in vitro pro-myogenic effects that are similar in potency to DHT.
In a castrated rat model, THG has demonstrable anabolic activity as it prevents the castration-
induced loss of FFM and levator ani [26] muscle mass. THG also prevents the atrophy of
prostate and seminal vesicles. Thus, THG displays both androgenic and anabolic properties in a
manner similar to testosterone enanthate. Therefore, THG is a bona fide androgen with anabolic
properties that meets the essential criteria for an anabolic steroid established by the Controlled
Substance Act [2].

We found the AR binding affinity of THG to be similar to that of DHT. Slight differences
in AR binding affinity reported by Labrie et al [35] might be related to the differences in
methods used to assess binding affinities, and the species differences in androgen receptor. Also,
the binding affinities estimated by using the LBD of androgen receptor might differ from those
derived by using the full length receptor. Using a yeast-based assay, Death et al, [34] have
reported that THG is a potent androgen with a transactivation potency that is ten times that of
testosterone. However, we do not know whether this yeast-based system expresses the repertoire
of co-regulators that is present in the mammalian androgen-responsive tissues. THG activates
many of the same genes activated by DHT in the levator ani [33]. However, it is possible that
THG might exert additional effects that are mediated through the progesterone receptor.

In orchidectomized rats, the anabolic potency of THG in the levator ani assay and its
androgenic potency in preventing castration-induced changes in prostate and seminal vesicle
weights appear to be similar to TE. While this manuscript was in preparation, Labrie et al [34]
reported that THG possesses only 20% of the potency of DHT in stimulating prostate, seminal
vesicle and levator ani muscle weight in the mouse. Because we used testosterone enanthate, a
direct comparison of our data to those reported by Labrie et al is not possible. Also, the observed
differences in in vivo potency may be related to the vehicle used for administering THG and
DHT, as the hydrophobicity of the vehicle can greatly affect the pharmacokinetics and
bioavailability of the compound. We recognize that an absolute quantitative comparison of the in
vivo potencies of THG and testosterone enanthate can not be made with the available data, as the
pharmacokinetics and bioavailability of THG in rats and mice are unknown. The 24-hour profile
of circulating THG concentrations depends not only on the administered dose but also on the
vehicle used; thus, the mode of administration, hydrophobicity of the vehicle used, and the
treatment regimen could affect greatly the observed in vivo activity.

THG is structurally related to gestrinone, a 19-nor progestin; it also has some
resemblance to trenbolone. Our molecular modeling studies revealed that the D ring of THG, an
important determinant of steroid specificity [25-29], displays unique stabilizing interactions with
AR. The interaction between AR and A ring of THG was similar to that between AR and A ring
of DHT, but both of the unique C17 and C18 substituents in THG had stabilizing interactions
with the AR. These data suggest that other D-ring modifications might confer higher affinity
and/or anabolic/androgenic potency because of these stabilizing interactions.

While steroid abuse by professional athletes and recreational bodybuilders has been
widely recognized since the 1950s, the synthesis and dissemination of novel designer steroids
such as THG has added new complexity to the detection and regulation of these compounds [16].
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