Pregnenolone

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Pregnenolone

Postby DIM » Tue Jun 10, 2008 4:11 am

Does anyone use pregnenolone instead of DHEA for nerve/myelin regeneration?
I have read that it works better as it can converted to DHEA and/or other hormones say testosterone, progesterone, estriol, estradiol etc through different pathways:
http://upload.wikimedia.org/wikipedia/c ... enesis.gif
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Postby gibbledygook » Tue Jun 10, 2008 6:31 am

Hi Dim,

I didn't know any of that but there's certainly plenty on PubMed on DHEA and nerve regeneration and here's one mentioning pregnenolone:
1: Growth Horm IGF Res. 2004 Jun;14 Suppl A:S18-33. Links
Local synthesis and dual actions of progesterone in the nervous system: neuroprotection and myelination.Schumacher M, Guennoun R, Robert F, Carelli C, Gago N, Ghoumari A, Gonzalez Deniselle MC, Gonzalez SL, Ibanez C, Labombarda F, Coirini H, Baulieu EE, De Nicola AF.
Inserm U488, 80 rue du Général Leclerc, 94276 Kremlin-Bicêtre, France. schuma@kb.inserm.fr

Progesterone (PROG) is synthesized in the brain, spinal cord and peripheral nerves. Its direct precursor pregnenolone is either derived from the circulation or from local de novo synthesis as cytochrome P450scc, which converts cholesterol to pregnenolone, is expressed in the nervous system. Pregnenolone is converted to PROG by 3beta-hydroxysteroid dehydrogenase (3beta-HSD). In situ hybridization studies have shown that this enzyme is expressed throughout the rat brain, spinal cord and dorsal root ganglia (DRG) mainly by neurons. Macroglial cells, including astrocytes, oligodendroglial cells and Schwann cells, also have the capacity to synthesize PROG, but expression and activity of 3beta-HSD in these cells are regulated by cellular interactions. Thus, Schwann cells convert pregnenolone to PROG in response to a neuronal signal. There is now strong evidence that P450scc and 3beta-HSD are expressed in the human nervous system, where PROG synthesis also takes place. Although there are only a few studies addressing the biological significance of PROG synthesis in the brain, the autocrine/paracrine actions of locally synthesized PROG are likely to play an important role in the viability of neurons and in the formation of myelin sheaths. The neuroprotective effects of PROG have recently been documented in a murine model of spinal cord motoneuron degeneration, the Wobbler mouse. The treatment of symptomatic Wobbler mice with PROG for 15 days attenuated the neuropathological changes in spinal motoneurons and had beneficial effects on muscle strength and the survival rate of the animals. PROG may exert its neuroprotective effects by regulating expression of specific genes in neurons and glial cells, which may become hormone-sensitive after injury. The promyelinating effects of PROG were first documented in the mouse sciatic nerve and in co-cultures of sensory neurons and Schwann cells. PROG also promotes myelination in the brain, as shown in vitro in explant cultures of cerebellar slices and in vivo in the cerebellar peduncle of aged rats after toxin-induced demyelination. Local synthesis of PROG in the brain and the neuroprotective and promyelinating effects of this neurosteroid offer interesting therapeutic possibilities for the prevention and treatment of neurodegenerative diseases, for accelerating regenerative processes and for preserving cognitive functions during aging.
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Good find!
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Postby cheerleader » Tue Jun 10, 2008 9:50 am

I hadn't heard of pregnenolone as a supplement. Seems like there is not as much known about it as a pre-cursor hormone and not as much research as DHEA. I would be careful in its usage- since it has been linked to increasing activity of glutamate receptors...very harmful for MSers.

"Pregnenolone also works the other side of the equation by increasing the activity of the NMDA (N-methyl-D-aspartate) subtype of glutamate receptors. Glutamate is a major excitatory neurotransmitter whose enhanced action recharges the brain and makes it more capable of handling the day’s activities."

Glutamate-stimulated peroxynitrite production in a brain-derived endothelial cell line is dependent on N-methyl-D-aspartate (NMDA) receptor activation
http://cat.inist.fr/?aModele=afficheN&cpsidt=18430185

Résumé / Abstract
There is accumulating and convincing evidence indicating a role for glutamate in the pathogenesis of the human demyelinating disease multiple sclerosis (MS). Studies in experimental autoimmune encephalomyelitis (EAE), the animal model of MS, demonstrate that pharmacological inhibition of specific glutamate receptors suppresses neurological symptoms and prevents blood-brain barrier (BBB) breakdown. The mechanisms through which glutamate influences BBB function during EAE remain unclear. Glutamate triggers the production of nitric oxide and superoxide, which can lead to the formation of peroxynitrite (ONOO-).

maybe a bit of caution is warranted?

AC
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Postby cheerleader » Tue Jun 10, 2008 10:10 am

One more abstract on pregnenolone and glutamate receptors-

Pregnenolone sulphate attenuates AMPA cytotoxicity on rat cortical neurons

Neuroactive steroids can modulate brain excitability by interaction with several neurotransmitter receptor-associated channels. These compounds may thus exert profound influences on excitotoxic injury, i.e. neuronal cell death triggered by over-activation of glutamate receptors. It has been reported that pregnenolone sulphate (PS) and pregnenolone hemisuccinate (PHS) augment N-methyl-d-aspartate (NMDA) neurotoxicity in rat cultured neurons.

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Postby DIM » Tue Jun 10, 2008 10:45 am

Thanks AC, I just wonder if pregnenolone is better choice from DHEA as DHEA may enhance cancer cells proliferation which isn't good what ever way you look at it!
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Postby cheerleader » Tue Jun 10, 2008 10:53 am

It's a tough call, Dimitris....
I had Jeff on too high a dose of dhea. He's now on 25mg. every other day, and he takes a hormonal break every month for a few days. We keep our eye on his PSA, since there is prostate cancer in his family.

He feels better on the dhea, and his testosterone is at a good level, and his PSA is normal. When you supplement with hormones and hormonal precursors, you have to keep your eye on serum levels, but I think it's worth it for better quality of life.

best to you and your wife, whatever you decide!
AC
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