Pregnenolone For Protection Against Melanoma

haidut

Member
Joined
Mar 18, 2013
Messages
17,435
Location
USA / Europe
Ray has written a few times on the topic of "moles" and how he treated his with DHEA, T3 and progesterone. While he did not mention pregnenolone, I always wondered if it would have a similar effect as animal studies with pregnenolone noted lack of melanoma in treated animals subjected to UV light. It looks like pregnenolone (sulfate) does indeed inhibit melanoma development and it does this by activating the so-called TRPM1 receptor. There are only a few known compounds that activate that receptor and one of them is being tried for melanoma.

Pregnenolone sulfate - Wikipedia, the free encyclopedia
"...In addition to its effects on ligand-gated ion channels, pregnenolone sulfate is an agonist of the sigma receptor,[2] as well as an activator of the TRPM1 and TRPM3 channels.[1] It may also interact with potassium channels and voltage-gated sodium channels."

TRPM1 - Wikipedia, the free encyclopedia
"...The protein encoded by this gene is a member of the transient receptor potential (TRP) family of non-selective cation channels. The expression of this protein is inversely correlated with melanoma aggressiveness, suggesting that it suppresses melanoma metastasis.[4] The expression of the TRPM1 gene is regulated by the Microphthalmia-associated transcription factor."

TRPM1 transient receptor potential cation channel subfamily M member 1 [Homo sapiens (human)] - Gene - NCBI
"...This gene encodes a member of the transient receptor potential melastatin subfamily of transient receptor potential ion channels. The encoded protein is a calcium permeable cation channel that is expressed in melanocytes and may play a role in melanin synthesis. Specific mutations in this gene are the cause autosomal recessive complete congenital stationary night blindness-1C. The expression of this protein is inversely correlated with melanoma aggressiveness and as such it is used as a prognostic marker for melanoma metastasis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2011]"
 

MCF

Member
Joined
Sep 7, 2015
Messages
55
Haidut: For the treatment of melanoma can Pansterone be taken orally (in juice)? If so what dose would you recommend?

Thank you much
 

haidut

Member
Thread starter
Joined
Mar 18, 2013
Messages
17,435
Location
USA / Europe
Haidut: For the treatment of melanoma can Pansterone be taken orally (in juice)? If so what dose would you recommend?

Thank you much

I think MelaNon would be a better supplement for topical use, and I would take pregnenolone orally as it has higher chance of raising pregnenolone sulfate (PS), which is what is needed for the melanoma effects. Pansterone contains comparatively low amount of pregnenolone and it is mostly there as an aromatase inhibitor to prevent DHEA from converting to estrogen, and also pregnenolone potentiates the effects of whatever steroid it is co-administered with, so that is another reason for its presence in Pansterone.
Also, here is an excerpt from the actual study, which says that both pregnenolone and PS have the same effects. Either way, loading up with oral pregnenolne is probably the best way to increase both pregnenolone and PS levels.

Pregnenolone Sulfate: From Steroid Metabolite to TRP Channel Ligand
"...TRPM3 is a polymodal ion channel activated by a variety of different stimuli like hypotonicity [100], sphingolipids [101], steroids [6,102], nifedipine [6], and heat [103]. The steroid-dependent modulation of TRPM3 is complex. Pregnenolone sulfate, pregnenolone and epipregnanolone sulfate stimulate TRPM3 activity whereas progesterone inhibits PregS-stimulated TRPM2 activity [6,102,104]. The concentration-response curves of PregS and pregnenolone reveal comparable potency of both steroids (Table 1), whereas both activating ligands showed dramatic differences in efficacy. The intrinsic activity of PregS is more than ten-fold higher than the intrinsic activity of pregnenolone [6]. With respect to the hydrophilicity of the sulfate moiety, it is interesting that TRPM3 is activated selectively by extracellular application of PregS, intracellular infusion of PregS via the patch pipette failed to induce TRPM3-mediated currents [6]. The activation of TRPM3 is remarkable as the temperature profile shows a continuous increase in TRPM3 activity in the range of 27 °C to 43 °C [103], which is contrast to TRPV1 showing increased activity beyond a threshold of 40 °C [105]. However, the most fascinating feature of the heat-dependent modulation of TRPM3 activity is the sensitization towards PregS [103]. At normal human body temperature, TRPM3 can be activated by PregS concentrations in the range of 100 to 500 nM corresponding to physiologic PregS serum concentrations (see above) [103]. Electrophysiological characterization revealed permeability of TRPM3 for calcium, sodium, magnesium, manganese and zinc ions [100,101,106,107]. Expression profile and subsequent functional analysis provides evidence for TRPM3 function in vascular smooth muscle contraction [108], modulation of glucose-induced insulin release from pancreatic islets [6,109], detection of noxious heat in dorsal root ganglia [103], and activation of oligodendrocytes and neurons in developing brains [91,110].
TRPM1, the founding member of the TRPM channel subfamily was discovered in a screen looking for transcriptional regulation in melanoma [92,111]. The absence of TRPM1 in malign melanoma guided the authors to name the TRP channel identified melastatin. Difficulties in cDNA cloning and expression as well as occurrence of many splice variants hampered the characterization of TRPM1 [112]. The protein was mainly studied in the context of melanocytes [113] until its role in mammalian phototransduction was discovered [114]. In electroretinograms (ERG) of TRPM1−/− mice the so-called b-wave, the measure for ON bipolar cells was missing [114]. Immunohistochemistry revealed expression of TRPM1 in rod ON bipolar cells and initiated a series of studies characterizing TRPM1 in the context of glutamate-induced signal transduction comprising metabotropic glutamic acid receptor (mGluR6), heteromeric Go proteins, and RGS proteins [115,116,117,118,119,120]. As TRPM1 like TRPM3 is activated by PregS [89] it is interesting to note the ability of retina for neurosteroidogenesis, which has been shown in rat retina [121]. Furthermore, it is possible that the neurotoxic effects in retina induced by PregS [122,123,124] are mediated by TRPM1-mediated calcium entry."

It also worth noting, that zinc was found to be a strong inhibitor of the TRPM1 channel, and as such may be unadvisable to use in people with melanoma.
http://www.jbc.org/content/286/14/12221.full

Given that most sunscreens have zinc oxide I wonder if this is may explain the dramatic increase in melanoma coinciding with increased sunscreen use...:shock:

Hey, @aguilaroja do you have any insight on that? I will ask my NIH buddies but any insight would be appreciated.
 
Last edited:

Kray

Member
Joined
Feb 22, 2014
Messages
961
I think MelaNon would be a better supplement for topical use, and I would take pregnenolone orally as it has higher chance of raising pregnenolone sulfate (PS), which is what is needed for the melanoma effects. Pansterone contains comparatively low amount of pregnenolone and it is mostly there as an aromatase inhibitor to prevent DHEA from converting to estrogen, and also pregnenolone potentiates the effects of whatever steroid it is co-administered with, so that is another reason for its presence in Pansterone.
Also, here is an excerpt from the actual study, which says that both pregnenolone and PS have the same effects. Either way, loading up with oral pregnenolne is probably the best way to increase both pregnenolone and PS levels.

Haidut,

For overall balance and health, do you recommend oral vs topical? If taken orally, would you suggest for women to take StressNon instead of Pansterone? Would the dosage for each product be the same for women as for men? Is it ok to take pregnenolone on an ongoing basis, since it is a hormone precursor, unlike progesterone or testosterone? (I'm referring to your recommended bottle dose vs. 100mg or higher referenced above.)

Thank you,
 
Similar threads
Thread starter Title Forum Replies Date
E Can Pregnenolone replace Progesterone temporarily during Pregnancy? Female Issues 1
O Pregnenolone Powder Won't Dissolve in DMSO Supplements, Pharmaceutical Drugs 0
V Pregnenolone, Progesterone, DHEA supplementation advice Supplements, Pharmaceutical Drugs 7
F Pregnenolone & or DHEA on TRT for anxiety&hair loss Ask For Help or Advice 4
M Pregnenolone supplementation causing hairloss Pregnenolone 10
ddjd progesterone causing headaches + poor sleep. pregnenolone completely relieves symptoms Ask For Help or Advice 11
Epistrophy Pregnenolone + Testosterone Base = All natural pain killer Experiments 24
Yon Your experience with progesterone, T3/T4 and pregnenolone Health 14
deliciousfruit Pregnenolone makes me suicidal Ask For Help or Advice 19
pauljacob Pregnenolone Gave Me Vertigo Pregnenolone 10
deliciousfruit Is pregnenolone safe for adolescents? Supplements, Pharmaceutical Drugs 4
haidut Oral pregnenolone as hormone replacement therapy (HRT) in humans Scientific Studies 16
ddjd ways to increase CYP11A activity other than K2MK4? Cholesterol→Pregnenolone Ask For Help or Advice 10
O Those Who Tried Oral Pregnenolone: Did You Notice A Facelift Effect? Polls 6
pauljacob Can I Break Open A Niacinamide, Pregnenolone Capsule? Supplements, Pharmaceutical Drugs 4
cjmorin Pregnenolone Hair Fall? Hair & Nails 16
cjmorin Pregnenolone Hair Fall? Hair & Nails 0
K I Took 100mg Pregnenolone ED For Years - Please Help Me Supplements, Pharmaceutical Drugs 63
E Pregnenolone Solo Ask For Help or Advice 5
B Central Serous Retinopathy / (Piracetam/Pregnenolone/TRT/Cortison) Health 21
R Pregnenolone Improving Posture/muscle Tightness? Supplements 11
J Male 25 / Pregnenolone 50mg - Hot Flashes - Raising Metabolism? Supplements, Pharmaceutical Drugs 2
E Philosopher AI About Pregnenolone Pregnenolone 11
E If Anyone Is Interested I'll Be Sharing COA Of Douglas Labs Pregnenolone Pharmaceutical Drugs 2
haidut Pregnenolone (P5) May Be Ergogenic And Helps Recovery From Exercise Scientific Studies 0
ScurveDream DHEA Or Pregnenolone To Combat Possible Caffeine-induced Stress? Ask For Help or Advice 8
Cecilia L. High Pregnenolone, High Progesterone, High Estradiol, Low D Female Issues 13
C Can Pregnenolone Make Fatigue Worse? Ask For Help or Advice 8
C Are Pregnenolone Capsules Safe To Take Every Day? Ask For Help or Advice 10
noqcks Eczema Cleared Up With Pregnenolone? Skin 12
D Why Does Low Dose Pregnenolone Affect Me So Powerfully? Pregnenolone 15
Light Micronized Pregnenolone Is Dissolving Well In Shea Butter Pregnenolone 3
haidut Pregnenolone (P5) - A New Osteoporosis Drug Scientific Studies 0
F Pregnenolone Makes Me Freezing Cold? Pregnenolone 1
haidut Pregnenolone Safe And Effective In Big Human Trial For Back Pain Scientific Studies 0
B Pregnenolone Supplementation Supplements, Pharmaceutical Drugs 0
B Impact From 25mg Pregnenolone Oral Daily On Progesterone And DHT Levels? Hormones 1
cyclops Why Does Ray Think Its Ok To Take Extremely Large Doses Of Pregnenolone? Pregnenolone 25
Moshi Pregnenolone And The GABA Paradox Thyroid and Hormones 15
S Pregnenolone And Androsterone Together? Supplements, Pharmaceutical Drugs 27
M Pregnenolone And Body Temp Supplements, Pharmaceutical Drugs 17
Peatogenic Can Pregnenolone Supplementation Raise Cortisol? Pregnenolone 7
fever257 First Time On Pregnenolone. All I Can Say Is Wow Ask For Help or Advice 10
haidut Pregnenolone (P5) Fully Prevents Testicular Atrophy Due To Steroid (ab)use Or High Estrogen Scientific Studies 55
B Pregnenolone + DHEA: Daily Or Weekly? Ask For Help or Advice 17
I Magnesium + Pregnenolone Insomnia, Sleep Issues 3
Lenny How Does One Use Pregnenolone/DHEA Powder? Supplements, Pharmaceutical Drugs 3
R Pregnenolone In Canada Ask For Help or Advice 2
J What Brand Of Pregnenolone Is Best To Take? Cortisol, Serotonin, Histamine 8
Lokzo PREGNENOLONE: What's Your Experience? Experiments 3

Similar threads

Top