Pregnenolone And Prostate Cancer

[haidut]

Yes this would be interesting.

See my response above.

 

[Braveheart]

Yep, here it is. Only one study, but they found increase in prostate cancer growth both in vitro and in vivo.
Pregnenolone stimulates LNCaP prostate cancer cell growth via the mutated androgen receptor. - PubMed - NCBI

The human equivalent dose was 3.5mg/kg and treatment was for 4 weeks. Again, in vitro and in vivo studies.

What does this mean for me, a 71 yr old, watching his prostate and taking two drops Pansterone every other day?

 

[goodandevil]

See my response above.

@haidut Do you have access to the full study? Also, you sell supplements with pregnenolone in them, so what are your feelings on this study? Also do you have any other studies verifying this connection you assert between pregnenolone and cancer; Ray has said that a lot of pregnenolone has impurities.

 

[haidut]

What does this mean for me, a 71 yr old, watching his prostate and taking two drops Pansterone every other day?

Probably not relevant as the study used oral administration and a dose of 300mg - 400mg daily.

 

[haidut]

@haidut Do you have access to the full study? Also, you sell supplements with pregnenolone in them, so what are your feelings on this study? Also do you have any other studies verifying this connection you assert between pregnenolone and cancer; Ray has said that a lot of pregnenolone has impurities.

See attached. I sincerely doubt the pregnenolone used in that study had impurities. It was obtained from a legitimate chemical vendor and likely of at least reagent-grade quality. If somebody knows what impurities in commercial pregnenolone can cause prostate cancer please share. I would be very interested in following up on that.
Now, that study used cell lines and inoculation of prostate cancer containing a "mutated" androgen receptor. Not sure how relevant this would be to a healthy prostate or if this receptor is present in all prostate cancers. But it is an interesting study nonetheless, especially the part that it shows pregnenolone being as potent as DHT and R1881 as agonist of that "mutated" androgen receptor.

 

[Wilfrid]

I would rather have a doubt regarding " Lca xenografts procedures " made in rodents.... as the raw materials used could certainly be the real source of impurities rather than the pregnenolone itself. Combining those exogenous impurities with the pregnenolone ( likely unreliable interactions ) can probably induce a very difficult reading ( or at least misleading... ) from the result of such kind of studies....

From:

In vitro and in vivo model systems used in prostate cancer research

...."Relevant to the topic of xenograft procedures, the issue of bioengineered materials should be discussed. Substances such as Matrigel™, polyethylene glycol (PEG), collagen and sponge are often used in the creation of a cell suspension pre-procedure to allow a microenvironment hospitable for cancer cell growth. There is no question that these materials are useful in rendering a more faithful tumor microenvironment both in xenograft and 3-dimensional (3D) culture models. However, it is still being discussed in the field about the effect that these materials have on gene expression profiles and responsiveness to androgen. Work by Lang et al. seems to indicate that Matrigel™ induces morphological changes that may be indicative of gene expression profile changes [107]. More recent studies have indicated more finely tuned materials such as PEG hydrogels, containing arginine-glycine-aspartate (RGD) and matrix metalloproteinase (MMP) cleavage sites, provide a microenvironment that better recapitulates native tissue environment [108]. This consideration should be made particularly if hormone sensitivity or drug discovery studies are being conducted."

Link to the above article:
http://www.jbmethods.org/jbm/article/download/63/45

Do you know by chance what kind of " substances " the authors used to realize their xenograft procedure in their in-vivo experiment?
I think they were using the Matrigel, no? Which made the authors conclusion not very reliable regarding the causative relation found between pregnenolone and prostate cancer cells.
And it could also certainly explain Ray's concerns and warnings about impurities when it comes to supplement exogenous hormones, as any impurities ( in the raw material itself during the manufacturing process, or indirectly/directly added during a clinical experiment ) could lead to a false medical interpretation ( early progesterone deceptive therapies come to mind ) and also unexpected results when it comes to oral supplementation for humans .

 

[Wilfrid]

More to come about the " matrigel "substance ":

Br J Cancer. 2001 Aug 17;85(4):590-9.
Prostate epithelial cell lines form spheroids with evidence of glandular differentiation in three-dimensional Matrigel cultures.
Lang SH1, Sharrard RM, Stark M, Villette JM, Maitland NJ.
Author information

Abstract
Normal (PNT2-C2) and metastatic (PC-3) prostate cell lines were grown in Matrigel to observe the effects on morphology and phenotype in comparison to monolayer culture. In monolayer cultures, PNT2-C2 showed typical round/cuboidal epithelial morphology, with tight cell associations, whereas in Matrigel they formed smooth spheroids, tightly packed with cells. In both monolayer and Matrigel, PNT2-C2 had a differentiated luminal epithelial phenotype with high expression of cytokeratin 8, prostate specific antigen (PSA), prostate specific membrane antigen (PSMA), E-cadherin and desmoglein. In contrast, PC-3 cells possessed an epithelial/mesenchyme morphology in monolayer with loose cell to cell contact and pseudopodial extensions. Immunohistochemical phenotyping indicated the cells were undifferentiated, expressing high levels of vimentin, beta1 integrin, CD44 and low expression of cytokeratin 8. In Matrigel they formed smooth and irregular spheroids, which had a lumen surrounded by a single cell layer. Matrigel also influenced the expression of PSA, PSMA and CD44. These results indicate that Matrigel culture can induce morphological differentiation of prostate cancer cells which initially had a basal phenotype."

I don't know if RP was right again on this but, at least regarding the link between pregnenolone and prostate cancer cells, I would probably give him a huge credit about his warning about impurities/contaminants used in supplements and during clinical experimentations ( and especially those made on rodents.)
To sum up my thoughts: the " impurities " that could lead to a false reading/wrong interpretation don't come from the pregnenolone itself but rather, in this case, to an added substance/culturing medium interacting in a negative way with the hormone/hormonal system.
Knowing this, it is hard for me to give any credits to this study.

 

[Makrosky]

Yep, here it is. Only one study, but they found increase in prostate cancer growth both in vitro and in vivo.
Pregnenolone stimulates LNCaP prostate cancer cell growth via the mutated androgen receptor. - PubMed - NCBI

The human equivalent dose was 3.5mg/kg and treatment was for 4 weeks. Again, in vitro and in vivo studies.

Thanks! Yeah it's quite of a big dose...

 

[goodandevil]

I would rather have a doubt regarding " Lca xenografts procedures " made in rodents.... as the raw materials used could certainly be the real source of impurities rather than the pregnenolone itself. Combining those exogenous impurities with the pregnenolone ( likely unreliable interactions ) can probably induce a very difficult reading ( or at least misleading... ) from the result of such kind of studies....

From:

In vitro and in vivo model systems used in prostate cancer research

...."Relevant to the topic of xenograft procedures, the issue of bioengineered materials should be discussed. Substances such as Matrigel™, polyethylene glycol (PEG), collagen and sponge are often used in the creation of a cell suspension pre-procedure to allow a microenvironment hospitable for cancer cell growth. There is no question that these materials are useful in rendering a more faithful tumor microenvironment both in xenograft and 3-dimensional (3D) culture models. However, it is still being discussed in the field about the effect that these materials have on gene expression profiles and responsiveness to androgen. Work by Lang et al. seems to indicate that Matrigel™ induces morphological changes that may be indicative of gene expression profile changes [107]. More recent studies have indicated more finely tuned materials such as PEG hydrogels, containing arginine-glycine-aspartate (RGD) and matrix metalloproteinase (MMP) cleavage sites, provide a microenvironment that better recapitulates native tissue environment [108]. This consideration should be made particularly if hormone sensitivity or drug discovery studies are being conducted."

Link to the above article:
http://www.jbmethods.org/jbm/article/download/63/45

Do you know by chance what kind of " substances " the authors used to realize their xenograft procedure in their in-vivo experiment?
I think they were using the Matrigel, no? Which made the authors conclusion not very reliable regarding the causative relation found between pregnenolone and prostate cancer cells.
And it could also certainly explain Ray's concerns and warnings about impurities when it comes to supplement exogenous hormones, as any impurities ( in the raw material itself during the manufacturing process, or indirectly/directly added during a clinical experiment ) could lead to a false medical interpretation ( early progesterone deceptive therapies come to mind ) and also unexpected results when it comes to oral supplementation for humans .

Wow! Excellent!

 

[goodandevil]

See attached. I sincerely doubt the pregnenolone used in that study had impurities. It was obtained from a legitimate chemical vendor and likely of at least reagent-grade quality. If somebody knows what impurities in commercial pregnenolone can cause prostate cancer please share. I would be very interested in following up on that.
Now, that study used cell lines and inoculation of prostate cancer containing a "mutated" androgen receptor. Not sure how relevant this would be to a healthy prostate or if this receptor is present in all prostate cancers. But it is an interesting study nonetheless, especially the part that it shows pregnenolone being as potent as DHT and R1881 as agonist of that "mutated" androgen receptor.

@haidut

Anything that irritates the intestine will increase risks for cancer of all types. Do you have any more studies on pregnenolone and cancer bro? This was one study, in which I noticed they were selling something: "our novel compounds designed to be an inhibitor of androgen synthesis, were potent inhibitors of the AR-mediated transcriptional activity induced by P(5), and were able to inhibit LNCaP-cell proliferation". Anyways this study was conducted back in 2000, have any more studies been published since then? This is one study, now no disrespect, i love the radio shows you did with danny, you're a fount of information, but ray has supppelied 5 studies against 5alphaprogesterone in which nothing is being sold. Plus Wilfrid has pointed out that the matrix material these cells are immersed in may make hormone assays unreliable. So, looking again at the bigger picture, I hear what you're saying: you're saying pregnenolone is associated with cancer as well, so that lends some doubt to the studies ray supplied on 5alphadh progesterone, but are those two contentions really comparable? Well I think it's good all the studies are out there so people can decide for themselves. Maybe 5-alpha dihydroprogesterone will be ten times as good as regular progesterone, but it's still experimental, so all the information, favorable or unfavorable, should be out there.

 

[haidut]

@haidut

Anything that irritates the intestine will increase risks for cancer of all types. Do you have any more studies on pregnenolone and cancer bro? This was one study, in which I noticed they were selling something: "our novel compounds designed to be an inhibitor of androgen synthesis, were potent inhibitors of the AR-mediated transcriptional activity induced by P(5), and were able to inhibit LNCaP-cell proliferation". Anyways this study was conducted back in 2000, have any more studies been published since then? This is one study, now no disrespect, i love the radio shows you did with danny, you're a fount of information, but ray has supppelied 5 studies against 5alphaprogesterone in which nothing is being sold. Plus Wilfrid has pointed out that the matrix material these cells are immersed in may make hormone assays unreliable. So, looking again at the bigger picture, I hear what you're saying: you're saying pregnenolone is associated with cancer as well, so that lends some doubt to the studies ray supplied on 5alphadh progesterone, but are those two contentions really comparable? Well I think it's good all the studies are out there so people can decide for themselves. Maybe 5-alpha dihydroprogesterone will be ten times as good as regular progesterone, but it's still experimental, so all the information, favorable or unfavorable, should be out there.

The study was not meant to discredit Ray's studies. User @Makrosky asked for it and I simply posted it. I am actually seriously considering cancelling the 5a-DHP until more is known about it. It is indeed only one study and I am not aware of any others that have verified its claims, even though quite a few recent studies (circa 2015 - 2016) cite it. Of course that does not prove anything.
Anyways, I think we are making this into a bigger deal than it is. One study does not prove anything until it is replicated independently.

 

[goodandevil]

It's lower than the one used for schizophrenia and bipolar disorder, so not that high. Also, it may challenge the idea that pregneno


The study was not meant to discredit Ray's studies. User @Makrosky asked for it and I simply posted it. I am actually seriously considering cancelling the 5a-DHP until more is known about it. It is indeed only one study and I am not aware of any others that have verified its claims, even though quite a few recent studies (circa 2015 - 2016) cite it. Of course that does not prove anything.
Anyways, I think we are making this into a bigger deal than it is. One study does not prove anything until it is replicated independently.

Agreed. Oh by the way I was going to agree with you on the pregnenolone purity, they got it from sigma I agree it's probably pure. Hopefully people will have a lot of experiences with 5adhp to post who knows maybe it's great? have a great day haidut. thanks for your energin by the way, i use it all the time. it's helped my uncle a lot, too (he has heart failure).

 

[haidut]

Agreed. Oh by the way I was going to agree with you on the pregnenolone purity, they got it from sigma I agree it's probably pure. Hopefully people will have a lot of experiences with 5adhp to post who knows maybe it's great? have a great day haidut. thanks for your energin by the way, i use it all the time. it's helped my uncle a lot, too (he has heart failure).

Oh wow, awesome! Any info on dosage and how often he uses it? If you can post that in the Energin thread it would be great.

 

[goodandevil]

Oh wow, awesome! Any info on dosage and how often he uses it? If you can post that in the Energin thread it would be great.

Will do ill ask him tonight.

 

[Obi-wan]

Just read the entire post plus the studies. I have advanced prostate cancer and am back on Firmagon which blocks LH and FSH. Tried to get off and the PSA went back up. The urologist is now recommending Xtandi which is an AR blocker. Even if the receptor is mutated I do not understand how androgens can cause cell proliferation. I thought only estrogen can do that. Pregnenolone, Progesterone, DHT are aromatase inhibitors. So what really is going on?

 

[Obi-wan]

I believe estrogen is involved in a mutated AR. Maybe through SHBG that binds to the receptor. @haidut care to comment? This should be right up your alley of expertise...

 

[jitsmonkey]

After asking some smart people some reasonably not stupid questions
I'm thinking this is just one study in a sea of rabidly contrdictory info re: Preg.

Conducted on castrated= very altered hormone mice.

SCID mice: “Also Known As: NOD scid, NOD SCID.
Mice homozygous for the severe combined immune deficiency spontaneous mutation Prkdcscid, commonly referred to as scid, are characterized by an absence of functional T cells and B cells, lymphopenia, hypogammaglobulinemia, and a normal hematopoietic microenvironment.” = horribly broken mice

Considering Preg is an "adaptive" substance requiring a live metabolism capable of responding in a reasonable way it would appear the test subjects are robbed of this potentiality. I'm gonna keep my good friend Preg around.

 

[haidut]

I believe estrogen is involved in a mutated AR. Maybe through SHBG that binds to the receptor. @haidut care to comment? This should be right up your alley of expertise...

Estrogen is directly mutagenic and carcinogenic. There is not even any need for SHBG to get involved.
Is estradiol a genotoxic mutagenic carcinogen? - PubMed - NCBI

 

[Frankdee20]

What happens if ingested Pregnenalone remains as PS, via bypassing Liver ? No androgen conversion I mean.

 

[Obi-wan]

Per Ray in Fats, functions & Malfunctions article SHBG binds with estrogen to try and keep it out of the cell or remove it from the cell. Free PUFA keeps it from binding estrogen. PUFA binds with proteins (receptors)and blocks them. So a mutated AR might be a blocked receptor by PUFA allowing estrogen to stay in the cell and not allowing any hormones in @haidut. I did not understand when he said "it's possible that SHBG's opposite behavior, entering the cell only when it carries no hormones, is a result of becoming less lipophilic when its loaded with estrogen" @ecstatichamster since you really liked that article.