Pregnenolone Stimulates The Thyroid

[haidut]

Pregnenolone is an activator of the so-called Pregnane X Receptor (PXR). Activators of this receptor has been shown to stimulate the excretion of toxic substances and lower cholesterol. This is one of the reasons Selye and his peers referred to pregnenolone and DHEA as "catatoxic" steroids. However, currently there is widespread belief in pharma industry circles that ordinary pregenolone has a half-life that is too short in order to be able to activate the receptor and maintain it active. In order to get around these imagined deficiencies of pregnenolone, a company synthesized a special type of pregnenolone called pregnenolone carbonitrile (PCN). It behaves identically to regular pregnenolone with the exception of having a much longer half-life. The important thing to note is that PCN is officially recongized as glucocorticoid receptor antagonist:
http://www.sigmaaldrich.com/catalog/pro ... &region=US
"...Pregnenolone-16α-carbonitrile (PCN) is a glucocorticoid receptor antagonist and a PXR (pregnane X receptor) activator."
I emphasize this point for the people who still think that pregnenolone is somehow pro-cortisol and will increase stress hormones. It won't, but I am sure the debate will continue. For the record, the other well-known glucocorticoid receotor antagonist is DHEA.
Anyways, Peat has written about the effects of pregnenolone on thyroid and several people have asked him to provide a study that confirms the pro-metabolic effects of pregnenolone. I don't know if he has provided a study, but here is one that shows a hefty human equivalent dose of about 30mg/kg powerfully stimulates the thyroid and increases T4 synthesis.

http://www.ncbi.nlm.nih.gov/pubmed/1203555

"...PCN, in daily doses of 20 mg/100 g per body weight exerted a marked stimulative effect on the rat thyroid. It was also found that the uptake of radioiodine in animals receiving PCN, was increased. Chromatographic investigations have shown that in PCN treated animals the biosynthesis of thyroid hormones was accelerated. There is evidence of histophysiological activation of the TSH cells of the adenohypophysis. It was concluded that there was no inhibition of the synthesis of thyroid hormones and that activation of the pituitary-thyroid axis under the influence of PCN, resulted from alteration of the peripheral metabolism of thyroxin."

 

[Dean]

Haidut, just a point of clarification. At least in my case when I talked about the potential negative cortisol effect of pregnenolone or DHEA, I meant the lowering of it. I mean, I know it's not good to be running on adrenals, but if you turn them off or way down then how will I function? Maybe other people are under the impression that pregnenolone raises cortisol, but maybe it is the same misunderstanding about what people mean about pregnenolone having a negative effect on cortisol? I don't know.

This is interesting though about pregnenolone stimulating thyroid. I'd seen that (or mimicking of thyroid) attributed to progesterone, which is why I surmised if I was going to try one or the other, it would be progesterone.

There I go breaking my self-imposed ban on posting in this section. OK, starting NOW-OW!

 

[haidut]

Haidut, just a point of clarification. At least in my case when I talked about the potential negative cortisol effect of pregnenolone or DHEA, I meant the lowering of it. I mean, I know it's not good to be running on adrenals, but if you turn them off or way down then how will I function? Maybe other people are under the impression that pregnenolone raises cortisol, but maybe it is the same misunderstanding about what people mean about pregnenolone having a negative effect on cortisol? I don't know.

This is interesting though about pregnenolone stimulating thyroid. I'd seen that (or mimicking of thyroid) attributed to progesterone, which is why I surmised if I was going to try one or the other, it would be progesterone.

There I go breaking my self-imposed ban on posting in this section. OK, starting NOW-OW!

No problem, I didn't mean you specifically. I just know that some people on the forum have repeatedly stated that pregnenolone raises their cortisol, but so far I have not seen studies backing this up or blood test results.
Yes, stopping adrenal function completely would not be advisable, especially in the absence of well-working thyroid.
Progesterone stimulates the thyroid, but so does DHEA (in smaller doses only). So, I wonder if the pregnenolone effect above is the result of conversion into progesterone and DHEA (which we know is what mostly happens to pregnenolone upon ingestion), or direct effect on thyroid. As Peat said cortisol inactivates T3 and inhibits synthesis of T4. So cortisol is antagonistic to thyroid function (more or less). If pregnenolone is indeed a cortisol antagonist then it is probably acting directly itself on thyroid

 

[jyb]

I had an initial reaction to pregne that was for sure something like cortisol or adrenalin. Tested on several brands. It then disappeared after a few days of supplementing and I've taken a lot of pregne since then, but I can see why people worried (as obviously they should if the stress reaction continues).

 

[haidut]

I had an initial reaction to pregne that was for sure something like cortisol or adrenalin. Tested on several brands. It then disappeared after a few days of supplementing and I've taken a lot of pregne since then, but I can see why people worried (as obviously they should if the stress reaction continues).

Pregnenolone is catatoxic, and if there is a lot of junk in your liver or somewhere else initially you may get this reaction that looks like cortisol but is in fact part of the detoxification process. However, in the absence of blood tests we have no way of knowing what was in your case, or anybody else's for that matter. As much as Peat thinks blood tests do not show the true state of health, they ar evaluable IMO in evaluating how a substance affects you. Especially if it is something that people are worried may be raising their cortisol or estrogen.

 

[ilovethesea]

So could pregnenolone be used as a surrogate for thyroid? What dose would be appropriate?

I have huge problems getting a consistent supply of T3 (I have to take it for life, as I only half my gland left). Doctors are a lost cause and we're not allowed to order our own meds here. I'm running out of options so looking for anything that will help me keep metabolism up.

Edited to add - not that pregnenolone is allowed here in Canada either, but I have a feeling it's easier to get in the country than - God forbid - thyroid supplement! It might as well be opium for the way it's restricted.

 

[haidut]

So could pregnenolone be used as a surrogate for thyroid? What dose would be appropriate?

I have huge problems getting a consistent supply of T3 (I have to take it for life, as I only half my gland left). Doctors are a lost cause and we're not allowed to order our own meds here. I'm running out of options so looking for anything that will help me keep metabolism up.

Edited to add - not that pregnenolone is allowed here in Canada either, but I have a feeling it's easier to get in the country than - God forbid - thyroid supplement! It might as well be opium for the way it's restricted.

In my post above I list the dose they used in the study. In another post here, they used pregnenolone in a human equivalent dose of 3.5mg/kg daily for 7 weeks to prevent obesity and increase thermogenesis and energy expenditure.
viewtopic.php?f=75&t=6902

 

[cantstoppeating]

I decided to take 300mg of pregnenolone (a dose for me that approximates 3.5mg/kg used in the above study) and within 5 minutes began to feel spaced out, dizzy, a racing heart beat, jittery/nervousness of hands and feet with a feeling of panic. Quickly, I reached for OJ and my bag of sucrose and began guzzling it down. The symptoms disappeared within 10 minutes.

The only other times I've experienced this was after taking large doses of aspirin during extended periods of fasting.

This time I was well nourished, so I don't how blood sugar factored into the experience.

Could the pregnenolone of acted as an immediate 'accelerator' of metabolism via T3, dramatically dropping blood sugar? Peat's general view of pregnenolone is that its effects are positive and overdosing is largely benign. Yet what I experienced was very close to the 'fight or flight' stress response.

More research is afoot.

 

[haidut]

I decided to take 300mg of pregnenolone (a dose for me that approximates 3.5mg/kg used in the above study) and within 5 minutes began to feel spaced out, dizzy, a racing heart beat, jittery/nervousness of hands and feet with a feeling of panic. Quickly, I reached for OJ and my bag of sucrose and began guzzling it down. The symptoms disappeared within 10 minutes.

The only other times I've experienced this was after taking large doses of aspirin during extended periods of fasting.

This time I was well nourished, so I don't how blood sugar factored into the experience.

Could the pregnenolone of acted as an immediate 'accelerator' of metabolism via T3, dramatically dropping blood sugar? Peat's general view of pregnenolone is that its effects are positive and overdosing is largely benign. Yet what I experienced was very close to the 'fight or flight' stress response.

More research is afoot.

Some of the human studies have reported that people may feel agitated/restless when taking pregnenolone. The proposed reason is the quick elevation in allopregnanolone, which may be anxiogenic in lower doses. The pregnenolone could have also stimulated the conversion of T4 into T3, or (more likely) triggered conversion of cholesterol into downstream steroids. Rapid increases in DHEA can give that feeling too. Kind hard to tell what happened without a blood test, but I bet at 300mg daily it will lower your cholesterol in about a week.

 

[MIP1950]

On my second week of taking 500mg of pregnenolone every morning. None of the problems that I encountered with 5 or 10mg. Body temp usually hits 98.0 by mid afternoon. Only lost 3 pounds and have yet to get below 140. I do have Testopel testosterone pellets implanted and their effect seemed to be fading after 5 weeks...until now. I hope those improvements continue. Also, just switched from Puritan's Pride preg capsules to pharma grade powder, though the preg capsules seemed to be working, even with magnesium stearate and silica.

My health has been in the toilet for so long that I believe it will take a couple of years on pregnenolone to see substantial changes.

 

[DaveFoster]

So what's the half-life on pregnenolone?

I know progesterone is 5-20 minutes, so maybe topical would be ideal.

 

[Jsaute21]

@cantstoppeating I took about 900 mg last night accidentally due to being in a rush. Felt fine on it somehow but never doing that again. Pulse never went above 70 but didn't drop too low either.

@haidut for those in somewhat compromised metabolic states, do you feel as if pregnenolone/andro are the safest steroids to sample? I seem to do better on them than pansterone in terms of heating up. As you and Peat have said, DHEA might be having a field day with tissue cortisol and estrogen.

 

[haidut]

@cantstoppeating I took about 900 mg last night accidentally due to being in a rush. Felt fine on it somehow but never doing that again. Pulse never went above 70 but didn't drop too low either.

@haidut for those in somewhat compromised metabolic states, do you feel as if pregnenolone/andro are the safest steroids to sample? I seem to do better on them than pansterone in terms of heating up. As you and Peat have said, DHEA might be having a field day with tissue cortisol and estrogen.

Pregnenolone in high doses can lower blood sugar due to conversion into pregnenolone sulfate (PS), which increases insulin production. I am not sure what the optimal dose would be but I agree that with people in compromised health pregnenolone and androsterone could be less risky as they should not lead to increased estrogen like DHEA. I personally feel pregnenolone in doses of 30mg - 50mg daily is probably optimal for most people unless there is a deficiency but if you feel better on a higher dose then do what feels best.

 

[encerent]

The problem a lot of people have with pregnenolone probably, then, has to do with the purity of the source.

 

[Jsaute21]

@encerent Health Natura and Idelabs have both worked decently for me.

 

[TubZy]

Pregnenolone is catatoxic, and if there is a lot of junk in your liver or somewhere else initially you may get this reaction that looks like cortisol but is in fact part of the detoxification process. However, in the absence of blood tests we have no way of knowing what was in your case, or anybody else's for that matter. As much as Peat thinks blood tests do not show the true state of health, they ar evaluable IMO in evaluating how a substance affects you. Especially if it is something that people are worried may be raising their cortisol or estrogen.

Could swollen lympnodes in the neck be a sign of that at all and what exactly is it detoxing? My liver enzymes were always high since quitting fin.

I had that for a few days when I first tried preg at very high doses, I just thought I was sick, could be coincidence.

 

[haidut]

Could swollen lympnodes in the neck be a sign of that at all and what exactly is it detoxing? My liver enzymes were always high since quitting fin.

I had that for a few days when I first tried preg at very high doses, I just thought I was sick, could be coincidence.

Well, finasteride is known to be hepatotoxic so that is not surprising. The swollen lymph nodes could be due to many issues, but usually are due to local infection like URTI or flu. If they stay persistently swollen through I would ask a doctor.

 

[Queequeg]

Is it ok to take pregnenolone by itself or is there a symbiotic effect with something like DHEA

 

[TubZy]

Well, finasteride is known to be hepatotoxic so that is not surprising. The swollen lymph nodes could be due to many issues, but usually are due to local infection like URTI or flu. If they stay persistently swollen through I would ask a doctor.

Thanks..I'm assuming caffeine is just as catatoxic as preg ore even more given its benefits for the liver, right?

 

[No_Energy]

Pregnenolone is an activator of the so-called Pregnane X Receptor (PXR). Activators of this receptor has been shown to stimulate the excretion of toxic substances and lower cholesterol. This is one of the reasons Selye and his peers referred to pregnenolone and DHEA as "catatoxic" steroids. However, currently there is widespread belief in pharma industry circles that ordinary pregenolone has a half-life that is too short in order to be able to activate the receptor and maintain it active. In order to get around these imagined deficiencies of pregnenolone, a company synthesized a special type of pregnenolone called pregnenolone carbonitrile (PCN). It behaves identically to regular pregnenolone with the exception of having a much longer half-life. The important thing to note is that PCN is officially recongized as glucocorticoid receptor antagonist:
http://www.sigmaaldrich.com/catalog/pro ... &region=US
"...Pregnenolone-16α-carbonitrile (PCN) is a glucocorticoid receptor antagonist and a PXR (pregnane X receptor) activator."
I emphasize this point for the people who still think that pregnenolone is somehow pro-cortisol and will increase stress hormones. It won't, but I am sure the debate will continue. For the record, the other well-known glucocorticoid receotor antagonist is DHEA.
Anyways, Peat has written about the effects of pregnenolone on thyroid and several people have asked him to provide a study that confirms the pro-metabolic effects of pregnenolone. I don't know if he has provided a study, but here is one that shows a hefty human equivalent dose of about 30mg/kg powerfully stimulates the thyroid and increases T4 synthesis.

[Effect of pregnenolone-16 alpha-carbonitrile on the activity of the rat thyroid gland and anterior pituitary]. - PubMed - NCBI

"...PCN, in daily doses of 20 mg/100 g per body weight exerted a marked stimulative effect on the rat thyroid. It was also found that the uptake of radioiodine in animals receiving PCN, was increased. Chromatographic investigations have shown that in PCN treated animals the biosynthesis of thyroid hormones was accelerated. There is evidence of histophysiological activation of the TSH cells of the adenohypophysis. It was concluded that there was no inhibition of the synthesis of thyroid hormones and that activation of the pituitary-thyroid axis under the influence of PCN, resulted from alteration of the peripheral metabolism of thyroxin."

Hi everybody, and @haidut,

I found it very interesting that PCN/"preg" could potentialy stimulate the thyroid. The study you posted pointed to that and said it resulted " from alteration of the peripheral metabolism of thyroxin."
I was interested and have been doing some reading and found this other study, wich makes me frustrated really. According to this study, and if understood it correctly, the stimulation would actually come from PCN/"preg" lowering T4 and subsequent excessive stimulation of the thyroid and production of TSH leading to Neoplasia(Tumor).
Frustrated, Not what I was hoping to find.. Maybe I got something wrong, I would like to hear what you guys think, @haidut ?

Thank you.

link to the full text : Promotion of Thyroid Tumors in Rats by Pregnenolone-16α-Carbonitrile (PCN) and Polychlorinated Biphenyl (PCB) | Toxicological Sciences | Oxford Academic

Promotion of Thyroid Tumors in Rats by Pregnenolone-16α-Carbonitrile (PCN) and Polychlorinated Biphenyl (PCB)
Promotion of Thyroid Tumors in Rats by Pregnenolone-16α-Carbonitrile (PCN) and Polychlorinated Biphenyl (PCB) | Toxicological Sciences | Oxford Academic
Published:

16 June 2004

Abstract
Pregnenolone-16α-carbonitrile (PCN) and Aroclor 1254 (PCB) both reduce serum thyroid hormone levels in rats, but only PCN consistently produces an increase in serum thyrotropin (TSH). PCN-mediated increases in TSH result in increased thyroid follicular cell proliferation and hyperplasia, which may represent early events on a morphological continuum leading to neoplasia. The purpose of this study was to assess whether PCN, a compound that increases serum TSH, and PCB, which does not increase TSH, promote thyroid tumors in a two-stage carcinogenesis model. Male SD rats were administered the thyroid tumor initiator diisopropanolnitrosamine (2.5 g/kg, sc), and after seven days were fed control diet, diet containing 1000 ppm PCN, or diet containing 100 ppm PCB for 19 weeks. Body weights were unaffected by PCN treatment, but were reduced 21% after 19 weeks of PCB treatment compared to control. PCN treatment significantly reduced serum T4 through week 3 before returning to control concentrations, whereas T4levels following PCB treatment fell below detection limits by week 3 and remained drastically reduced through week 19. TSH concentrations in PCN-treated rats increased three-fold at week 2, then declined to near control values at week 19. After one week of PCB treatment, TSH concentrations reached nearly twice that of controls, and were sustained until week 6. The incidence of thyroid follicular cell proliferative lesions, including cystic and follicular hyperplasia, cystic and follicular adenoma, and follicular carcinoma, was significantly increased following PCN treatment, but not following PCB treatment. PCB treatment caused an increase in thyroid carcinomas (4 of 22 rats) not associated with the proliferative-type lesions produced by PCN, despite an increase in TSH serum concentrations. In conclusion, PCN appears to promote thyroid tumors in a manner consistent with known effects of excessive TSH stimulation. However, thyroid carcinomas stemming from PCB treatment indicate that separate mechanisms exist for the production of thyroid cancer in rodents by chemicals classically considered microsomal enzyme inducers.