Guest guest Posted July 22, 2000 Report Share Posted July 22, 2000 In this abstract the researchers mention several different mechanisms by which pregnenolone might influence memory and learning. None of them would preclude increased production of cortisol as a possible negative side effect of pregnenolone supplementation. [Models for the study of memory and neurosteroids] [Les modeles d'etude de la memoire et les neurosteroides.] J Soc Biol 1999;193(3):299-306 Mathis C; Meziane H; Ungerer A [Find other articles with these Authors] Laboratoire d'Ethologie et de Neurobiologie, URA 1295 CNRS, Universite Louis Pasteur, Strasbourg, France. mathisc@.... The steroids dehydroepiandrosterone sulfate (DHEA-S) and pregnenolone sulfate (Preg-S) are naturally synthetized in the brain. They improve short term and long term memory performances in a variety of learning tasks and models of amnesia in rodents. DHEA-S and Preg-S modulate GABAergic and glutamatergic synaptic transmission through direct interactions with GABA-A, NMDA and/or sigma 1 membrane receptors. In addition, these two neurosteroids facilitate the release of acetylcholine and modulate synaptic plasticity phenomena in cerebral structures, such as the hippocampus, known to play a role in learning and memory processes. The possible links between these actions and the promnestic effects of DHEA-S and Preg-S are discussed in the present review. -gts Quote Link to comment Share on other sites More sharing options...
Guest guest Posted July 22, 2000 Report Share Posted July 22, 2000 >...None of them would preclude increased production of cortisol as a possible negative side effect of pregnenolone supplementation. Non sequiter.... doesn't say a thing about the it. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted July 22, 2000 Report Share Posted July 22, 2000 Nijusan and all, > >...None of them would preclude increased production of cortisol as a possible >> negative side effect of pregnenolone supplementation. > Non sequiter.... doesn't say a thing about the it. huh? None of the possible means described in the abstract by which preg might enhance memory preclude the possibility that preg supplementation increases production of cortisol. I have no idea why you call that a non sequiter. The preg advertisement you quoted claimed that preg might increase memory by *inhibiting* cortisol, but these academic researchers proposed four different means by which it does so *without* any obvious reliance on inhibiting cortisol. That is why I posted it -- the abstract demonstrates the incompleteness and perhaps even the error of the claims made in the preg advertisement that you posted. The problem remains.. Why did Dale begin to feel fatigued after supplementing with preg? As preg is a precurser to cortisol, excessive cortisol would certainly explain his experience. I've yet to hear a better explanation. I once took a very large dose of preg, by the way. I swallowed about one gram of preg powder mixed in juice. I felt very tense or stressed out for several hours, which was exactly the opposite experience that I had anticipated. For some reason or another I had anticipated a calming effect from a large dose of preg. Like Dale's fatigue, I suspect the stress I experienced could have been due to a surge in cortisol. Dr Maher posits a theory about how stress depletes pregnenolone, which is certainly plausible though I suspect unproven. However even if true it does not negate or preclude the possibility that preg supplementatiion can increase production of cortisol. The relevant biochemistry looks something like this: Cholesterol to Pregnenolone to Cortisol and DHEA -gts Quote Link to comment Share on other sites More sharing options...
Guest guest Posted July 22, 2000 Report Share Posted July 22, 2000 > excessive cortisol would certainly explain his experience. So, where's confirmatory evidence preg supplimentation _does_ increase se cortisol? And thereby explain Dales fatigue? You're guessing. I'm relying on non-scholarly sources. Apparently, Dr. Mahers lesson #5 will be available after August, 2000. We'll have a better notion of this 'steal syndrome' then. Gotta' say yr interpretation in support of increased cortisol thereby seems intuitively appealling. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted July 22, 2000 Report Share Posted July 22, 2000 > > I once took a very large dose of preg, by the way. I swallowed about one > gram of preg powder mixed in juice. I felt very tense or stressed out for > several hours, Wouldn't taking a heroic dose of anything make you kinda' nervous? Would me. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted July 22, 2000 Report Share Posted July 22, 2000 Anecdotal, anyway. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted July 22, 2000 Report Share Posted July 22, 2000 Nijusan, > > excessive cortisol would certainly explain his experience. > > > So, where's confirmatory evidence preg supplimentation _does_ increase > se cortisol? The biochemical pathway is already well known. Preg is a precursor to cortisol and the presence of precursors tends to promote production of the associated metabolites. I'd like to see a single example of a hormone that works in a manner *opposite* to this principle, as you have proposed may be the case with preg/cortisol. Can you give me a single example? >And thereby explain Dales fatigue? You're guessing. I'm offering a theory to explain the facts, Nijusan. It is a theory supported by general principles by which precursors and their metabolites interact, as stated above. Do you have a better theory to explain the facts? If so then I'd like to hear it. Why do you suppose Dale began to feel fatigued after supplementing with preg? Why did I feel stressed out for several hours after ingesting a large dose of it? (And no, I was not nervous about taking the large dose. I have no qualms about doing little experiments on myself with health supplements. And, as I mentioned, I actually expected that it would have the exact *opposite* effect. So there was clearly no placebo or mental tricks going on here.) -gts Quote Link to comment Share on other sites More sharing options...
Guest guest Posted July 22, 2000 Report Share Posted July 22, 2000 gordon wrote: > Can you give me a single example? Systemic IGF-1 also has hypothalamic and pituitary regulatory targets. The negative feedback loops cause down-regulation of GH secretion directly at the pituitary. The longer positive feedback loop, involving IGF-1 regulation at the hypothalamus, stimulates the secretion of somatostatin (SS, also called growth hormone-inhibiting hormone, GIH), which in turn inhibits the secretion of growth hormone by the pituitary. The latter is a relatively unusual negative feed-forward regulatory process. In addition, a shorter negative feedback loop is shown that involves direct IGF-1 action on the pituitary, leading to down-regulation of GH secretion. Similar feedback loops exist for all the major endocrine hormones, and many subtle nuances modulate each regulatory loop. http://web.indstate.edu/thcme/mwking/peptide-hormones.html > > >And thereby explain Dales fatigue? You're guessing. > > I'm offering a theory Nope. A 'hypothesis'. " Supraphysiologic serum cortisol levels from supplimentary pregnenolone must explain this case of Dale feeling fatigued " ? This is what you wanna' go to the mat over? Jeez, I'll hold yr coat for ya'! Quote Link to comment Share on other sites More sharing options...
Guest guest Posted July 22, 2000 Report Share Posted July 22, 2000 gordon wrote: > Can you give me a single example? Systemic IGF-1 also has hypothalamic and pituitary regulatory targets. The negative feedback loops cause down-regulation of GH secretion directly at the pituitary. The longer positive feedback loop, involving IGF-1 regulation at the hypothalamus, stimulates the secretion of somatostatin (SS, also called growth hormone-inhibiting hormone, GIH), which in turn inhibits the secretion of growth hormone by the pituitary. The latter is a relatively unusual negative feed-forward regulatory process. In addition, a shorter negative feedback loop is shown that involves direct IGF-1 action on the pituitary, leading to down-regulation of GH secretion. Similar feedback loops exist for all the major endocrine hormones, and many subtle nuances modulate each regulatory loop. http://web.indstate.edu/thcme/mwking/peptide-hormones.html > > >And thereby explain Dales fatigue? You're guessing. > > I'm offering a theory Nope. A 'hypothesis'. A guess, however well-educated. " Supraphysiologic serum cortisol levels from supplimentary pregnenolone must explain this case of Dale feeling fatigued " ? This is what you wanna' go to the mat over? Jeez, I'll hold yr coat for ya'! Quote Link to comment Share on other sites More sharing options...
Guest guest Posted July 22, 2000 Report Share Posted July 22, 2000 A brief scan of the web after entering " pregnenolone " in a search engine reveals that pregnenolone is often advertised as an aid to those suffering from allergies and arthritis. The described mechanism is via its conversion to cortisone. Here we have a case of an advertiser promoting a negative as a positive. (unless of course you really have problems with allergies and arthritis, in which case cortisone may be just what the doctor ordered.) I once had an elderly client who took massive doses of cortisone in his shoulder for arthritis. The shots left him 'freaked out' for days. -gts Quote Link to comment Share on other sites More sharing options...
Guest guest Posted July 22, 2000 Report Share Posted July 22, 2000 Nijusan, your example below is not valid. GH is not a metabolic precursor to IGF-1 and GHRH is not a precursor to GH. IGF-1 is synthesized in the liver in response to GH, but the GH molecule is not itself a direct " ingredient " to the synthesis IGF-1. I've often been annoyed by the incorrect use of the word " precursor " on this mailing list and elsewhere. Another common error is to state that glutamine and other amino acids and peptides that stimulate release of GH are " precursors " to GH. They are not precursors. The proper term for them is " secretagogue " . GH has a secretagogue-like relationship to IGF-1 -- not a precursor relationship. -gts Re: prognenolone > gordon wrote: > > > Can you give me a single example? > > Systemic IGF-1 also has hypothalamic and pituitary > regulatory targets. The negative feedback loops cause > down-regulation of GH secretion directly at the > pituitary. The longer positive feedback loop, involving > IGF-1 regulation at the hypothalamus, stimulates the > secretion of somatostatin (SS, also called growth > hormone-inhibiting hormone, GIH), which in turn > inhibits the secretion of growth hormone by the > pituitary. The latter is a relatively unusual negative > feed-forward regulatory process. In addition, a shorter > negative feedback loop is shown that involves direct > IGF-1 action on the pituitary, leading to > down-regulation of GH secretion. Similar feedback > loops exist for all the major endocrine hormones, and > many subtle nuances modulate each regulatory loop. > > http://web.indstate.edu/thcme/mwking/peptide-hormones.html > > > > > > > > >And thereby explain Dales fatigue? You're guessing. > > > > > > > I'm offering a theory > > > Nope. A 'hypothesis'. > > > " Supraphysiologic serum cortisol levels from supplimentary pregnenolone > must explain this case of Dale feeling fatigued " ? > > > This is what you wanna' go to the mat over? > > Jeez, I'll hold yr coat for ya'! > > ------------------------------------------------------------------------ > Make new friends, find the old at Classmates.com: > 1/7075/14/_/164625/_/964325990/ > ------------------------------------------------------------------------ > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted July 22, 2000 Report Share Posted July 22, 2000 > The described mechanism is via its conversion > to cortisone. This is a pretty shitting " citation " of literature, bucko. > I once had an elderly client who took massive doses of cortisone in his > shoulder for arthritis. The shots left him 'freaked out' for days. Bud, are you inviting me to make a guess about yr elderly client? Forget it. _Off Topic_ Quote Link to comment Share on other sites More sharing options...
Guest guest Posted July 22, 2000 Report Share Posted July 22, 2000 gordon wrote: > > Nijusan, your example below is not valid. GH is not a metabolic precursor to > IGF-1 and GHRH is not a precursor to GH. > > IGF-1 is synthesized in the liver in response to GH, but the GH molecule is > not itself a direct " ingredient " to the synthesis IGF-1. > > I've often been annoyed by the incorrect use of the word " precursor " on this > mailing list and elsewhere. Another common error is to state that glutamine > and other amino acids and peptides that stimulate release of GH are > " precursors " to GH. They are not precursors. The proper term for them is > " secretagogue " . GH has a secretagogue-like relationship to IGF-1 -- not a > precursor relationship. > > -gts > > Re: prognenolone > > > gordon wrote: > > > > > Can you give me a single example? > > > > Systemic IGF-1 also has hypothalamic and pituitary > > regulatory targets. The negative feedback loops cause > > down-regulation of GH secretion directly at the > > pituitary. The longer positive feedback loop, involving > > IGF-1 regulation at the hypothalamus, stimulates the > > secretion of somatostatin (SS, also called growth > > hormone-inhibiting hormone, GIH), which in turn > > inhibits the secretion of growth hormone by the > > pituitary. The latter is a relatively unusual negative > > feed-forward regulatory process. In addition, a shorter > > negative feedback loop is shown that involves direct > > IGF-1 action on the pituitary, leading to > > down-regulation of GH secretion. Similar feedback > > loops exist for all the major endocrine hormones, and > > many subtle nuances modulate each regulatory loop. > > > > http://web.indstate.edu/thcme/mwking/peptide-hormones.html > > > > > > > > > > > > > > >And thereby explain Dales fatigue? You're guessing. > > > > > > > > > > > > I'm offering a theory > > > > > > Nope. A 'hypothesis'. > > > > > > " Supraphysiologic serum cortisol levels from supplimentary pregnenolone > > must explain this case of Dale feeling fatigued " ? > > > > > > This is what you wanna' go to the mat over? > > > > Jeez, I'll hold yr coat for ya'! > > > > ------------------------------------------------------------------------ > > Make new friends, find the old at Classmates.com: > > 1/7075/14/_/164625/_/964325990/ > > ------------------------------------------------------------------------ > > > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted July 22, 2000 Report Share Posted July 22, 2000 " Progesterone is formed by oxidation of the alcohol at C3 to a ketone, then isomerization of the double bond from D5 to D4. DHEA to androstenedione and pregnenolone to cortisol use the same reaction sequence of oxidation then isomerization. " In simpler terms: pregnenolone converts to cortisol in a manner very similar to that by which DHEA converts to testosterone and other androgens. see: http://www.neurosci.pharm.utoledo.edu/MBC3320/steroid_hormones.htm -gts Quote Link to comment Share on other sites More sharing options...
Guest guest Posted July 22, 2000 Report Share Posted July 22, 2000 [Oooops! Sorry for that last one!=== to save you having to scroll... here's the kernal: Quote G.:> > I'd like to see a single example of a hormone that > works in a manner *opposite* to this principle, as you have proposed may > be > the case with preg/cortisol. Can you give me a single example? > > This was your challenge, no?. I met it. Now stifle till you got some > evidence to _Prove_ what you propose: To Wit: > > > " Supraphysiologic serum cortisol levels from supplimentary pregnenolone > > must explain this case of Dale feeling fatigued " ? > > Is this or is this not what you are insisting upon? > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted July 22, 2000 Report Share Posted July 22, 2000 > In simpler terms: pregnenolone converts to cortisol in a manner very similar > to that by which DHEA converts to testosterone and other androgens. > Never disputed it. Quote Link to comment Share on other sites More sharing options...
Guest guest Posted July 22, 2000 Report Share Posted July 22, 2000 Nijusan, > Quote G.:> > > I'd like to see a single example of a hormone that > > works in a manner *opposite* to this principle, as you have proposed > > may be the case with preg/cortisol. Can you give me a single example? > > > > > > This was your challenge, no?. I met it. No you did not meet it. Read my paragraph again, which you quote in part above. The principle is as follows, and this time I will capitalize my words: " Preg is a precursor to cortisol and THE PRESENCE OF PRECURSORS TENDS TO PROMOTE PRODUCTION OF THE ASSOCIATED METABOLITES. " In this case the associated metabolites are progesterone, dhea and cortisol. The example you gave of a supposed exception to the principle above concerns feedback relationships between GHRH, GH and IGF-1. None of these three hormones are precursors to any of these three hormones, so how could your example be even remotely relevant to the principle above? It neither proves it nor disproves it. GH does not act as a chemical component in the synthesis of IGF-1 and is therefore not a *precursor* to it. GH merely SIGNALS the liver to produce IGF-1. -gts Quote Link to comment Share on other sites More sharing options...
Guest guest Posted July 22, 2000 Report Share Posted July 22, 2000 Rigging for silent running: bedtime hereabouts.... Quote Link to comment Share on other sites More sharing options...
Guest guest Posted July 22, 2000 Report Share Posted July 22, 2000 > > In simpler terms: pregnenolone converts to cortisol in a manner very >> similar to that by which DHEA converts to testosterone and other > > androgens. > > > Never disputed it. Okay great! I'm glad you don't dispute it. Now then, why do men take DHEA? One very common reason is to promote production of testosterone(T). Is it effective for this purpose? Yes! Studies abound which show that DHEA supplementation increases T levels. This is because the presence of precursors (in this case dhea) tends to promote production of the associated metabolites (in this case andro, which in turn converts to T). Now then read the quoted sentence at the top of this letter and try to surmise what might happen if we take pregnenolone instead of DHEA. -gts Quote Link to comment Share on other sites More sharing options...
Guest guest Posted July 23, 2000 Report Share Posted July 23, 2000 DHEA tends to suppress cortisol. Balance of all sterol hormones is essential. Excess or inadequate both cause dysfunction. They all are interactive. R , MD Quote Link to comment Share on other sites More sharing options...
Guest guest Posted July 23, 2000 Report Share Posted July 23, 2000 Nijusan, So far I want to say that this battle is going much more civilly than some in the past. Also the info both of you are putting out is great. Nijusan, great link below. I have been looking for something like this to get a better understanding of steroids. Gordo, also thanks. I hadn't thought about the cortisol and that would explain quite a bit. One thing I would like to add about my experience with preg. is that I also think my bodies production of T went down at the same time which is why I the fatigue was so pronounced. It was a month until I started feeling better so everyone out there be careful with this stuff. Cycle cycle cycle. Also fyi this was about two years ago and I don't think it has anything to do with my present condition. On another note--I have been on the hGH for about two months now and am not getting the quality sleep that others have talked about. I still wake up at three in the morn and either have to take something to get me back to sleep or it takes an hour or two to fall back asleep if I can. I have been experimenting and think I have seen a pattern that may improve my sleep, and that being the less exogenous products I take, the better I sleep. Any comments would be appreciated I think for the next week I am going to swear off everything exogenous (except T and hGH) and see if I am correct. I will report back. Thanks to both of you and please keep this civil. I don't think there is anyway to tell who is correct on this and then it probably wouldn't apply to everyone anyway. Thanks, Dale Nijusan wrote: > gordon wrote: > > > Can you give me a single example? > > Systemic IGF-1 also has hypothalamic and pituitary > regulatory targets. The negative feedback loops cause > down-regulation of GH secretion directly at the > pituitary. The longer positive feedback loop, involving > IGF-1 regulation at the hypothalamus, stimulates the > secretion of somatostatin (SS, also called growth > hormone-inhibiting hormone, GIH), which in turn > inhibits the secretion of growth hormone by the > pituitary. The latter is a relatively unusual negative > feed-forward regulatory process. In addition, a shorter > negative feedback loop is shown that involves direct > IGF-1 action on the pituitary, leading to > down-regulation of GH secretion. Similar feedback > loops exist for all the major endocrine hormones, and > many subtle nuances modulate each regulatory loop. > > http://web.indstate.edu/thcme/mwking/peptide-hormones.html > > > > > >And thereby explain Dales fatigue? You're guessing. > > > > > I'm offering a theory > > Nope. A 'hypothesis'. A guess, however well-educated. > > > " Supraphysiologic serum cortisol levels from supplimentary pregnenolone > must explain this case of Dale feeling fatigued " ? > > This is what you wanna' go to the mat over? > > Jeez, I'll hold yr coat for ya'! > > ------------------------------------------------------------------------ > Missing old school friends? Find them here: > 1/7079/14/_/164625/_/964326020/ > ------------------------------------------------------------------------ > > Quote Link to comment Share on other sites More sharing options...
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