Pregnenolone and Prostate Cancer

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Pregnenolone and Prostate Cancer

Unread postby j. » Sat Mar 16, 2013 2:54 pm

According to this study, pregnenolone can make prostate cancer worse.

Pregnenolone stimulates LNCaP prostate cancer cell growth via the mutated androgen receptor.


Abstract
Pregnenolone (P(5)), a common precursor of many steroids, is present in the blood of normal adult men at concentrations of 1-3 nM. In vitro, P(5) was found to stimulate LNCaP-cell proliferation 7-8-fold at a physiological concentration (2 nM), and 3-4-fold at a subphysiological concentration (0.2 nM). Growth stimulation at the 2-nM concentration was comparable with that of the androgen, dihydrotestosterone at its physiological concentration (0.5 nM; 9-10-fold increase in cell number). To determine whether P(5) or its metabolites were mediating this growth response, LNCaP cells were incubated with [3H]P(5) and high-performance liquid chromatography (HPLC) was performed. After a 48-h exposure, two unidentified metabolites were detected. Although, the P(5) metabolites slightly increased LNCaP-cell growth in vitro, their effect was significantly less than P(5) alone, suggesting that the growth stimulation was mediated by P(5) itself. We further showed that P(5) sustained its proliferative activity in vivo and stimulated the growth of LNCaP-tumor xenografts in intact male SCID mice as well as in castrated animals. In order to determine whether P(5) was binding to a specific site in LNCaP cells, receptor binding studies were performed. Scatchard analysis predicted for a single class of binding sites with K(d)=1.4 nM. Studies were performed to determine the effects of P(5) on transcription mediated by wild-type and LNCaP androgen receptors. P(5) was shown to activate transcription through the LNCaP androgen receptor (AR), but not the wild-type AR. This implies that P(5) most likely stimulates LNCaP-cell proliferation through binding to the cellular mutated AR present in LNCaP cells. We have also demonstrated that drugs designed to be antagonists of the androgen, progesterone and estrogen receptors, and one of 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. These findings suggest that some prostate cancer patients who appear to become hormone-independent may have tumors which are stimulated by P(5) via a mutated AR and that these patients could benefit from treatment with antiestrogens, antiprogestins, or with some of our novel androgen synthesis inhibitors.

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Re: Pregnenolone and Prostate Cancer

Unread postby jag2594 » Tue Mar 19, 2013 5:20 pm

j. wrote:According to this study, pregnenolone can make prostate cancer worse.

Pregnenolone stimulates LNCaP prostate cancer cell growth via the mutated androgen receptor.


Abstract
Pregnenolone (P(5)), a common precursor of many steroids, is present in the blood of normal adult men at concentrations of 1-3 nM. In vitro, P(5) was found to stimulate LNCaP-cell proliferation 7-8-fold at a physiological concentration (2 nM), and 3-4-fold at a subphysiological concentration (0.2 nM). Growth stimulation at the 2-nM concentration was comparable with that of the androgen, dihydrotestosterone at its physiological concentration (0.5 nM; 9-10-fold increase in cell number). To determine whether P(5) or its metabolites were mediating this growth response, LNCaP cells were incubated with [3H]P(5) and high-performance liquid chromatography (HPLC) was performed. After a 48-h exposure, two unidentified metabolites were detected. Although, the P(5) metabolites slightly increased LNCaP-cell growth in vitro, their effect was significantly less than P(5) alone, suggesting that the growth stimulation was mediated by P(5) itself. We further showed that P(5) sustained its proliferative activity in vivo and stimulated the growth of LNCaP-tumor xenografts in intact male SCID mice as well as in castrated animals. In order to determine whether P(5) was binding to a specific site in LNCaP cells, receptor binding studies were performed. Scatchard analysis predicted for a single class of binding sites with K(d)=1.4 nM. Studies were performed to determine the effects of P(5) on transcription mediated by wild-type and LNCaP androgen receptors. P(5) was shown to activate transcription through the LNCaP androgen receptor (AR), but not the wild-type AR. This implies that P(5) most likely stimulates LNCaP-cell proliferation through binding to the cellular mutated AR present in LNCaP cells. We have also demonstrated that drugs designed to be antagonists of the androgen, progesterone and estrogen receptors, and one of 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. These findings suggest that some prostate cancer patients who appear to become hormone-independent may have tumors which are stimulated by P(5) via a mutated AR and that these patients could benefit from treatment with antiestrogens, antiprogestins, or with some of our novel androgen synthesis inhibitors.

Link


In a ray peat interview he talks about how male pattern baldness was not associated with androgens that everyone seems to think, but with estrogen and prolactin. Estradiol is converted from Testosterone, and high prolactin and pituitary tumors need estrogen. Pregnenolone being the precursor to all steroids, will be convert into the disease causing hormones that cause cancer.
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Re: Pregnenolone and Prostate Cancer

Unread postby jyb » Tue Mar 19, 2013 7:22 pm

jag2594 wrote: In a ray peat interview he talks about how male pattern baldness was not associated with androgens that everyone seems to think, but with estrogen and prolactin. Estradiol is converted from Testosterone, and high prolactin and pituitary tumors need estrogen. Pregnenolone being the precursor to all steroids, will be convert into the disease causing hormones that cause cancer.


Doesn't the pregnelonone conversion depend on diet and metabolism?
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Re: Pregnenolone and Prostate Cancer

Unread postby Isadora » Thu Mar 21, 2013 4:54 pm

jyb wrote:Doesn't the pregnelonone conversion depend on diet and metabolism?


It does, but it also depends on a person's circumstances and level of stress.

Unless you are this Yoga Master retired in a climate controlled cave, fully knowledgeable in the hormonal pathways and dedicated completely to influencing those, you cannot control what the supplemental pregnenolone will do in your body. And even the said guru would have to sleep, eventually, and then, who knows what nightmares he may have and how big of a cortisol steal happens, etc.

:) :2cents
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Re: Pregnenolone and Prostate Cancer

Unread postby jag2594 » Thu Mar 21, 2013 10:32 pm

jyb wrote:
jag2594 wrote: In a ray peat interview he talks about how male pattern baldness was not associated with androgens that everyone seems to think, but with estrogen and prolactin. Estradiol is converted from Testosterone, and high prolactin and pituitary tumors need estrogen. Pregnenolone being the precursor to all steroids, will be convert into the disease causing hormones that cause cancer.


Doesn't the pregnelonone conversion depend on diet and metabolism?


I was giving an example of one scenario, but no, hormonal imprinting, prenatal stress, environmental conditions all contribute to stress hormones.
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Re: Pregnenolone and Prostate Cancer

Unread postby Isadora » Mon Mar 25, 2013 4:03 pm

Anyway, the study mentions pregnenolone in one's own body producing the cancer-causing metabolites. Maybe the supplemental kind doesn't cascade into P5, one can always hope, right? :roll: I don't know, I'm very skeptical at this point of all these hormones. And the fast paced level of new discoveries related to them is not good news, in my book. What isn't yet known could kill us, too. I will stop all experiments with this, "face lifting" effect and other such mundane goodies aren't worth it.
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Re: Pregnenolone and Prostate Cancer

Unread postby jyb » Mon Mar 25, 2013 4:41 pm

Isadora wrote:Anyway, the study mentions pregnenolone in one's own body producing the cancer-causing metabolites. Maybe the supplemental kind doesn't cascade into P5, one can always hope, right? :roll: I don't know, I'm very skeptical at this point of all these hormones. And the fast paced level of new discoveries related to them is not good news, in my book. What isn't yet known could kill us, too. I will stop all experiments with this, "face lifting" effect and other such mundane goodies aren't worth it.


Not saying you're wrong but that's just one study. You can also find recent studies showing PUFAs are wonderful. You could email RP to comment on it if you have doubts like you have now? Please post his response here if you do.
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Re: Pregnenolone and Prostate Cancer

Unread postby Isadora » Mon Mar 25, 2013 5:28 pm

jyb wrote:Not saying you're wrong but that's just one study. You can also find recent studies showing PUFAs are wonderful.

It's a study that echoes MANY others. Together, they make the case that hormones have effects we are far from fully understanding, let alone control, and at the current level of knowledge, taking those supplements amounts to pretty reckless self-experimentation. If Peat resorted to it and he had no issues, good for him. For males it may be easier, especially after 60, as he suggests.

It's not the same as with PUFAs. I consider hormones to be much more dangerous substances than PUFAs ever could aspire to be considered. My father ate PUFAs since they were invented and he has no health issues to speak of. He still eats PUFAs. I don't, and I experience pains and have Hashimoto's. PUFAs are not something to obsess about while filling your bodies with "bio-identical" hormones.
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Re: Pregnenolone and Prostate Cancer

Unread postby Bryan » Thu Apr 11, 2013 5:20 pm

I know this is an old-ish thread, so sorry about this but....

It says cancer cell *proliferation* as if that was the main problem- cells growing too much. No mention of pregnenolone inducing cancer. That's the typical assumption when it comes to cancer, that it's abnormal growth that's the problem, not respiration or aneuploidy or any of the things that most scientists think are essential facets of cancer.

"We have also demonstrated that drugs designed to be antagonists of the androgen, progesterone and estrogen receptors, and one of our novel compounds designed to be an inhibitor of androgen synthesis..."

I think that might mean they have a drug they want to market? This was from the *Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine* after all.

And there's a lot of talk about receptors, which Peat says is mostly misleading stuff if I recall correctly.
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Re: Pregnenolone and Prostate Cancer

Unread postby sladerunner69 » Thu Aug 01, 2013 5:55 am

If Peat claims mpb to be a result of elevated estrogen and prolactin, and not androgens, then why is his own head of hair not the perfect specimen? Hasn't the man been meticulously avoiding estrogen and the other stress hormones since the 60's? The only compatible explanation I can think of would be that his hairline drastically receded during his young adult life, and then, once he got his dietary protocol in order, he was able to maintain his 30-40 yr old hairline. I find this scenario hard to believe considering it would implicate him being the first man to "beat mpb" naturally, and then not care enough to let anyone else know.
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