liveonearth (liveonearth) wrote,


3α,5β-tetrahydroprogesterone (3α,5β-THP)
endogenous steroid hormone, also prohormone (cannot be patented)
synthesized from cholesterol via P450scc in mitochondria
synthesis controlled by ACTH, FSH, LH from pituitary

INDICATIONS (none substantiated by science in humans)
memory enhancement
adrenal fatigue
vision: colors
sexual enjoyment, libido
boosts memory in rodents
menopausal symptoms (hot flashes), PMS

is neuroactive(anxiolytic), found and synthesized in brain
affects synaptic functioning, is neuroprotective, enhances myelinization
sulfate ester of preg being investigated for cognitive and memory function
also being considered as tx for schizo
preg is positive allosteric modulator of GABAa receptor (anxiolytic effect)
sulfated is negative allosteric modulator of same receptor
sulfated form also activates TRPM3 ion channel
in hepatocytes and pancretic islets-->insulin release
how do we control how sulfated it is in the brain???

pregnenolone-->17-OH pregnenolone (via CYP17A1, 17α-hydroxylase) and progesterone
17OH Preg-->DHEA (via desmolase)
DHEA-->androstenedione-->testosterone and estrone
estrone-->E2, E3

progesterone-->mineralocorticoids: aldosterone and glucocorticoids: cortisol

poorly documented
hair loss

physical exam, LFTs, bloop pressure

oral, bioavailability questionable
1-5mg SL
do not take high doses

Chronic pregnenolone effects in normal humans: attenuation of benzodiazepine-induced sedation.
Psychoneuroendocrinology. 2004. Meieran SE, Reus VI, Wolkowitz OM. University of California, San Francisco School of Medicine, San Francisco, CA,
In two preliminary studies, we sought to characterize tolerability and psychotropic effects of pregnenolone in humans. In Study 1, 17 normal volunteers received pregnenolone and placebo for 4 weeks each (15 mg PO per day x2 weeks followed by 30 mg PO per day x2 weeks, vs. placebo x4 weeks) in a within-subject, double-blind, cross-over design, with a 4 week drug-free washout period separating the two arms. Subjects' behavioral responses were assessed at the beginning and end of the 4-week pregnenolone arm and the 4-week placebo arm. Pregnenolone was generally well-tolerated but, by itself, had no significant effects on mood, memory, self-rated sleep quality or subjective well-being. In Study 2, 11 subjects from Study 1 received a single dose of diazepam (0.2 mg/kg PO) immediately following completion of Study 1 in order to assess, in a between groups design, the impact of 4-weeks' pre-treatment with pregnenolone (N=5) vs. placebo (N=6) on the acute sedative, amnestic and anxiolytic effects of this benzodiazepine. Pregnenolone-pretreated subjects showed significantly less sedation following diazepam; this effect was clinically apparent. Diazepam's amnestic effects were non-significantly attenuated, and ratings of anxiety were unaffected. These pilot data, based on small samples, raise the possibility that chronically administered pregnenolone antagonizes certain acute effects of benzodiazepines and may enhance arousal via antagonist or inverse agonist actions at the benzodiazepine/GABA(A) receptor complex. Further larger-scale pregnenolone studies, utilizing a broader range of doses and experimental conditions, are warranted.
Tags: anxiety, brain, dhea, estrogen, hormones, memory, nervous system, progesterone, schizophrenia, testosterone

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