[Grant]

Sledge posted this over in his fourm, since this is part of your new product, just wondering your opinions on the findings of this study.
------

1: J Endocrinol. 2004 Jan;180(1):125-33. Related Articles, Links


Forskolin up-regulates aromatase (CYP19) activity and gene transcripts in the human adrenocortical carcinoma cell line H295R.

Watanabe M, Nakajin S.

Department of Biochemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan. masatada@hoshi.ac.jp

A number of conditions related to sex-reversal in boys and men and precocious puberty in girls are caused by estrogen-secreting adrenal tumors. In these tumors, cytochrome P450 aromatase (aromatase) that is encoded in the CYP19 gene is expressed at high levels. To investigate the molecular mechanism of aromatase expression in these adrenal tumors, we characterized the activity, gene transcript and genomic promoter region of aromatase in the human adrenocortical carcinoma cell line H295R. Aromatase activity and the transcript of the CYP19 gene were highly up-regulated by forskolin, but not by dexamethasone. The results from exon I-specific reverse transcriptase (RT)-PCR and the transfection of reporter constructs suggested that promoter I.3 and promoter II were activated in H295R. Deletion and mutation analysis suggested that cAMP response element-like sequence (CLS) and steroidogenic factor-1 (SF-1) motif, were critical for the activation of promoter II. The results of this work should provide the basis for the molecular analysis of aromatase expression in adrenocortical cells.

PMID: 14709151 [PubMed - indexed for MEDLINE]

[Syr]

The write-up about forskolin on SM website is excellent.

It sounds like an awesome substance to preserve muscle mass while cutting or during PCT.
Also, they suggest the intake of Rolipram stacked with it. Being it available in europe (hehe), I'm tempted to try this combo.

[BodyWizard]

Grant - beat me to it!
Syr - agreed - excellent enticement re: forskolin

I'd really like to get some knowledgeable opinions on the pros & cons here.

[USPLabs]

Originally Posted by Grant

Sledge posted this over in his fourm, since this is part of your new product, just wondering your opinions on the findings of this study.
------

1: J Endocrinol. 2004 Jan;180(1):125-33. Related Articles, Links


Forskolin up-regulates aromatase (CYP19) activity and gene transcripts in the human adrenocortical carcinoma cell line H295R.

Watanabe M, Nakajin S.

Department of Biochemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan. masatada@hoshi.ac.jp

A number of conditions related to sex-reversal in boys and men and precocious puberty in girls are caused by estrogen-secreting adrenal tumors. In these tumors, cytochrome P450 aromatase (aromatase) that is encoded in the CYP19 gene is expressed at high levels. To investigate the molecular mechanism of aromatase expression in these adrenal tumors, we characterized the activity, gene transcript and genomic promoter region of aromatase in the human adrenocortical carcinoma cell line H295R. Aromatase activity and the transcript of the CYP19 gene were highly up-regulated by forskolin, but not by dexamethasone. The results from exon I-specific reverse transcriptase (RT)-PCR and the transfection of reporter constructs suggested that promoter I.3 and promoter II were activated in H295R. Deletion and mutation analysis suggested that cAMP response element-like sequence (CLS) and steroidogenic factor-1 (SF-1) motif, were critical for the activation of promoter II. The results of this work should provide the basis for the molecular analysis of aromatase expression in adrenocortical cells.

PMID: 14709151 [PubMed - indexed for MEDLINE]

Nandi will be over to answer this with science in no time!

ceosm

[BodyWizard]

[nandi]

Originally Posted by BodyWizard

I am not sure how applicable data taken from a tumor cell line that already expresses high amounts of aromatase is to overall estrogen production in the body of a normal human. In the case of breast cancer, tumors express high amounts of so called promoter II. Promoter II is involved in the production of estrogen via aromatase and is not the promoter found in normal (noncancerous) breast tissue. In normal breast tissue and in adipose tissue, so called promoter I.4 is responsible for aromatase induction. Promoter II is sensitive to cAMP elevation by forskolin whereas I have never seen any data supporting a role by forskolin in promoter I.4 expression. So one must use caution when attempting to extrapolate data obtained from tumor cell lines to normal tissue.

Here I am quoting from the abstract in the post that started this thread:

"The results from exon I-specific reverse transcriptase (RT)-PCR and the transfection of reporter constructs suggested that promoter I.3 and promoter II were activated in H295R"

So we see that promoter I.4 is not involved here, whereas the promoters I.3 and II, which are forskolin sensitive are expressed. So this is not a good model for the effects of forskolin on aromatase in normal tissue, especially adipose tissue, the primary site of aromatase in the human male.

One would expect some increase in estrogen while taking forskolin, regardless of the tumor data, since as I reported in my product writeup, forskolin seems to increase testosterone production directly at the testicular level and at the hypothalamic level by increasing GnRH production. This extra testosterone will serve as a substrate for the increased production of estrogen by aromatase.

I've also written a great deal on the beneficial aspects of estrogen as far as cardiovascular health is concerned. Moreover,studies have shown estrogen to positively affect cognition, and since the estrogen receptor as well as aromatase is present in skeletal muscle, estrogen no doubt plays some as yet unknown role in muscle physiology.

I am not a believer in suppressing estrogen, except in the case of the development of gynecomastia. For those of you who belong to the opposite camp, and wish to suppress estrogen at all cost, it is a simple matter to take an aromatase inhibitor or SERM while taking forskolin

[Grant]

Thanks alot, I didnt understand the study so I was curious as to what it meant. You sure do know your stuff.

[BodyWizard]

thanks for coming in, nandi!

so, you're saying:
1 - the study has no relevance to the actions of forskolin in the normal male physiology;
2 - what extra estrogen may be engendered by the forskolin is: a) negligible, and b) outweighed by the reduction in overall fatty mass & attendant aromatase production therein.

Have I got that right?

[size]

Great to see nandi posting here. I have always enjoyed reading his posts.

[nandi]

Originally Posted by BodyWizard

thanks for coming in, nandi!

so, you're saying:
1 - the study has no relevance to the actions of forskolin in the normal male physiology;
2 - what extra estrogen may be engendered by the forskolin is: a) negligible, and b) outweighed by the reduction in overall fatty mass & attendant aromatase production therein.

Have I got that right?

It's possible that forskolin could activate the promoter I.4 found in adipose tissue, but I have never seen any evidence for it. And you make the excellent point that even if forskolin did elevate aromatase in normal adipose tissue (again for which there is no evidence), the fat loss from forskolin would very likely make the whole thing a wash, leading to little if any increase in net aromatase. On the other hand, if forskolin has no effect on promoter I.4, as the lack of any supporting data suggests, then fat loss will lead to less aromatase and a possible drop in estrogen production. But as I mentioned, there is also an increase in testosterone with forskolin use, so it's also possible that even if a drop in aromatase is seen, the higher levels of substrate (testosterone) could keep estrogen levels normal or possibly even slightly elevated.

So all that is just a complicated way of saying, yes, you've got it right BodyWizard.

[USPLabs]

Originally Posted by nandi

It's possible that forskolin could activate the promoter I.4 found in adipose tissue, but I have never seen any evidence for it. And you make the excellent point that even if forskolin did elevate aromatase in normal adipose tissue (again for which there is no evidence), the fat loss from forskolin would very likely make the whole thing a wash, leading to little if any increase in net aromatase. On the other hand, if forskolin has no effect on promoter I.4, as the lack of any supporting data suggests, then fat loss will lead to less aromatase and a possible drop in estrogen production. But as I mentioned, there is also an increase in testosterone with forskolin use, so it's also possible that even if a drop in aromatase is seen, the higher levels of substrate (testosterone) could keep estrogen levels normal or possibly even slightly elevated.

So all that is just a complicated way of saying, yes, you've got it right BodyWizard.

From personal opinion, My estrogen levels get out of whack real quick on a prolonged androgen cycle. I been using cAMPHIBOLIC for over 4 months straight. I gained nearly 18lbs of muscle and lost a considerable amount of fat(the best shape of my life) so estrogen if effected did not effect my effects negatively(lol).

ceosm

[Alpha Dog]

Originally Posted by USPLabs

From personal opinion, My estrogen levels get out of whack real quick on a prolonged androgen cycle. I been using cAMPHIBOLIC for over 4 months straight. I gained nearly 18lbs of muscle and lost a considerable amount of fat(the best shape of my life) so estrogen if effected did not effect my effects negatively(lol).

ceosm

Just to get this straight, you are saying you used cAMPHIBOLIC for four months immediately following an androgen cycle and still gained 18lbs of muscle?

[USPLabs]

Originally Posted by bow

Just to get this straight, you are saying you used cAMPHIBOLIC for four months immediately following an androgen cycle and still gained 18lbs of muscle?

I wish! I have not been on a AAS cycle for over 7 months and that cycle main purpose was weight loss. I have not "bulked" in over a year.

ceosm

[Truck]

Originally Posted by USPLabs

I wish! I have not been on a AAS cycle for over 7 months and that cycle main purpose was weight loss. I have not "bulked" in over a year.

ceosm

WHAT???

you: "I been using cAMPHIBOLIC for over 4 months straight. I gained nearly 18lbs of muscle and lost a considerable amount of fat(the best shape of my life) so estrogen if effected did not effect my effects negatively(lol)."

if you did NOT in fact gain those 18lbs from camphibolic, then you should NOT present your responses in this manner, as it is deceitful if not intended to mean what it appears to mean....not that we dont take your results with a grain of salt as you are the person who stands to gain most from sales...

just clarify, please.

also, what's a good forskolin dose? nandi, feel free to answer if you're available. and can anyone give me those studies which show forskolin to increase testosterone...love to peruse 'em.

[USPLabs]

Originally Posted by Truck

WHAT???

you: "I been using cAMPHIBOLIC for over 4 months straight. I gained nearly 18lbs of muscle and lost a considerable amount of fat(the best shape of my life) so estrogen if effected did not effect my effects negatively(lol)."

if you did NOT in fact gain those 18lbs from camphibolic, then you should NOT present your responses in this manner, as it is deceitful if not intended to mean what it appears to mean....not that we dont take your results with a grain of salt as you are the person who stands to gain most from sales...

just clarify, please.

also, what's a good forskolin dose? nandi, feel free to answer if you're available. and can anyone give me those studies which show forskolin to increase testosterone...love to peruse 'em.

I am stating facts my friend. 4 months of great trianing, diet and cAMP 18lbs is not a miracle. If some insinuate it was done just on cAMP, My greatest apology, but most are aware that diet and training are paramount with any regimen even anabolic steroids. I have gained 10 lbs easily on creatine, diet and training. Why does 18bls get the sarcastic "what" response. Your 200% correct, I benefit from all sales.

I am experiementing with 180mg of forskolin a day but that is way above the recommended dose. Not giving all the credit to forskolin, the cissus is also a great natural anabolic! The studies are referenced at the end of the cAMP articl at synergy.