Pregnenolone's Potential Benefits..
What is pregnenolone?

Pregnenolone, a steroid, is synthesized in the gonads, adrenal gland and brain, from cholesterol.
It is a precursor for the biosynthesis of steroid hormones in adrenal gland, such as
mineralocorticoid aldosterone, glucocorticoid cortical, dehydroepiandrosterone (DHEA) and
progesterone, in ovary, such as estrogens and progesterone, in testis, such as testosterone.
While, pregnenolone and its metabolite pregnenolone sulfate found in the brain and central
nervous system are generally called as neurosteroids. [1]

Pregnenolone's Potential Health Benefits
Neurosteroids, such as pregnenolone (PREG), dehydroepiandrosterone (DHEA), and their
sulfates (PREGS and DHEAS) are reported to have a modulatory effect on neuronal excitability
and synaptic plasticity. They also have many other functions associated with neuroprotection,
response to stress, mood regulation, and cognitive performance. Furthermore, these
neurosteroids have been linked to, and their levels are altered in, neuropsychiatric disorders. [6]

Alzheimer's Disease
Many neuroendocrinological studies stressed the neuroprotective role of neurosteroids although
it has been suggested that the inhibition of pregnenolone and pregnenolone sulfate synthesis can
delay neuronal cell death. In a study, pregnenolone showed a dose-dependent protective effect
against Abeta peptide in rat PC-12 cells. [7] A few studies showed that pregnenolone benefits
older animals such as 24-month-old rats in term of memory enhancement by stimulating
acetylcholine release in the adult hippocampus. Alteration of cerebral plasticity was found in aged
cognitive disorders, particularly Alzheimer’s disease.  Unfortunately, human studies do not show
such benefits. [2]

Central acetylcholine neurotransmission is known to be involved in the regulation of memory
processes and is affected in normal aging and severely altered in human neurodegenerative
pathologies like Alzheimer's disease. Researchers demonstrated that central infusion of
pregnenolone sulfate dramatically increased neurogenesis. In the central nervous system,
acetylcholine neurotransmission is also involved in the modulation of sleep-wakefulness cycle,
and particularly the paradoxical sleep (PS). [3] The stimulation was probably induced via an
negative modulation of the gamma-aminobutyrate (GABA) and a positive allotter modulator at the
N-methyl-D-asparatate (NMDA) receptor. [1]

Pregnenolone may benefit people at risk of manic and depressive symptoms
In an investigation, 70 participants with bipolar disorder or recurrent major depressive disorder
and history of substance abuse/dependence (abstinent for > or =14days prior to enrollment) were
randomly assigned to receive pregnenolone (titrated to 100mg/day) or placebo for 8 weeks.
Findings suggest that pregnenolone use may be associated with some improvement in manic
and depressive symptoms, but not cognition in depressed patients with a history of substance
use. [5]

Problem? Side Effects? Unwanted Effects?
Pregnenolone appeared to be safe and well tolerated. [5] Researchers from Universidad
Nacional de Cuyo, Argentina, showed that pregnenolone sulfate (Preg-S) impairs rats' memory
for novel object recognition when injected in lateral septum (1.2 microM). [4]

[1] PDR Health, June 10, 2007 [2] Vallée M, et al, Role of pregnenolone, dehydroepiandrosterone and their sulfate esters on learning and
memory in cognitive aging.Brain Res Brain Res Rev. 2001 Nov;37(1-3):301-12.[3] Mayo W, et al, Individual differences in cognitive
aging: implication of pregnenolone sulfate.Prog Neurobiol. 2003 Sep;71(1):43-8. [4] Nanfaro F, Cabrera R, Bazzocchini V, Laconi M,
Yunes R., Pregnenolone sulfate infused in lateral septum of male rats impairs novel object recognition memory. Pharmacol Rep. 2010
Mar-Apr;62(2):265-72. [5] Osuji IJ, Vera-Bolaños E, Carmody TJ, Brown ES. Pregnenolone for cognition and mood in dual diagnosis
patients. Psychiatry Res. 2010 Jul 30;178(2):309-12. Epub 2010 May 21. [6] Ritsner MS Pregnenolone, dehydroepiandrosterone, and
schizophrenia: alterations and clinical trials. CNS Neurosci Ther. 2010 Spring;16(1):32-44. [7] Akan P, Kizildag S, Ormen M, Genc S,
Oktem MA, Fadiloglu M. Pregnenolone protects the PC-12 cell line against amyloid beta peptide toxicity but its sulfate ester does not.
Chem Biol Interact. 2009 Jan 15;177(1):65-70. Epub 2008 Sep 24.
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