"Pregnenolone sulfate" from_date:2012

Pregnenolone sulfate potentiates tetrodotoxin-resistant Na(+) channels to increase the excitability of dural afferent neurons in rats. Although peripheral administration of pregnenolone sulfate (PS) has been reported to produce pronociceptive effects, the mechanisms by which PS modulates the excitability of nociceptive neurons are poorly understood. Here, we report on the excitatory role of PS

Comparison of pregnenolone sulfate, pregnanolone and estradiol levels between patients with menstrually-related migraine and controls: an exploratory study. Neurosteroids affect the balance between neuroexcitation and neuroinhibition but have been little studied in migraine. We compared the serum levels of pregnenolone sulfate, pregnanolone and estradiol in women with menstrually-related migraine and controls and analysed if a correlation existed between the levels of the three hormones and history of migraine and age. Thirty women (mean age ± SD: 33.5 ± 7.1) with menstrually-related migraine (MM group) and 30 aged- matched controls (mean age ± SD: 30.9 ± 7.9) participated in the exploratory study. Pregnenolone sulfate and pregnanolone serum levels were analysed by liquid chromatography

Adrenocorticotropin Acutely Regulates Pregnenolone Sulfate Production by the Human Adrenal in Vivo and in Vitro. Dehydroepiandrosterone sulfate (DHEAS) is the most abundant steroid in human circulation, and adrenocorticotropic hormone (ACTH) is considered the major regulator of its synthesis. Pregnenolone sulfate (PregS) and 5-androstenediol-3-sulfate (AdiolS) have recently emerged as biomarkers

Gonadotropin-Releasing Hormone Stimulates the Biosynthesis of Pregnenolone Sulfate and Dehydroepiandrosterone Sulfate in the Hypothalamus. The sulfated neurosteroids pregnenolone sulfate (Δ(5)PS) and dehydroepiandrosterone sulfate (DHEAS) are known to play a role in the control of reproductive behavior. In the frog Pelophylax ridibundus, the enzyme hydroxysteroid sulfotransferase (HST

matched neurotypical controls (CTRL, n = 16). Collected plasma served for detection of conjugated and unconjugated steroids using gas chromatography tandem-mass spectrometry. We observed higher levels of steroids modulating ionotropic receptors, especially, GABAergic steroids and pregnenolone sulfate in ASD group. Concentration of many steroids throughout the pathway tend to be higher in ASD girls

in meningeal nerves suggests a potential interplay between both signalling systems. Compared to other members of the TRP family, TRPM3 channels have a high sensitivity to sex hormones and to the endogenous neurosteroid pregnenolone sulfate (PregS). The predominantly female sex hormones estrogen and progesterone, of which the levels drop during menses, act as natural inhibitors of TRPM3 channels, while PregS

or vehicle (sesame oil), and neurosteroid levels were measured in serum and cerebral tissue using liquid chromatography-electrospray tandem mass spectrometry after treatment. Pregnenolone sulfate, pregnenolone, progesterone, 5α-dihydroprogesterone, and allopregnanolone peripheral levels were massively increased by trilostane. With the only exception of hippocampal pregnenolone sulfate, the other

across all sleep phenotype domains except for SDB and EDS phenotypes. Several metabolites were associated with multiple sleep phenotypes, from a few domains. Glycochenodeoxycholate, vanillyl mandelate (VMA) and 1-stearoyl-2-oleoyl-GPE (18:0/18:1) were associated with the highest number of sleep phenotypes, while pregnenolone sulfate was associated with all sleep phenotype domains except for sleep

, Pregnenolone-sulfate, and N-(3-Hydroxybutanoyl)-L-homoserine lactone showed diagnostic efficiency of 98%(AUC=0.98[0.95-1.0]) and segregate ALF patients predisposed to early mortality (log-rank<0.05). On validation using HRMS and five machine learning algorithms in test cohort-1 (plasma and paired one-drop blood), the metabolome panel showed >92% accuracy/sensitivity and specificity for prediction

overload and by enhanced responses to the neurosteroid ligand pregnenolone sulphate, when co-expressed with wild-type TRPM3 in mammalian cells. The antiseizure medication primidone, a known TRPM3 antagonist, reduced the increased basal activity of all mutant channels. These findings establish gain-of-function of TRPM3 as the cause of a spectrum of autosomal dominant neurodevelopmental disorders

peptide and their cell bodies in L6-S1 dorsal root ganglion. Activation of TRPM3 in the bladder wall by its specific agonist pregnenolone sulphate or CIM0216 induced spontaneous bladder pain, calcitonin gene-related peptide release, and neurogenic inflammation that was evidenced by edema, plasma extravasation, inflammatory cell accumulation, and mast cell infiltration. In CYP rats, pretreatment

. Of the 21 metabolites in presurgical blood that were associated with risk of persistent postsurgical pelvic pain, 19 metabolites, which were mainly lipid metabolites, were associated with increased risk. Only 2 metabolites-pregnenolone sulfate (odds ratio = 0.64, 95% confidence interval = 0.44-0.92) and fucose (odds ratio = 0.69, 95% confidence interval = 0.47-0.97)-were associated with decreased risk

IS from SMs were asymmetrical and symmetrical dimethylarginine, pregnenolone sulfate, and adenosine. Together, these 4 metabolites differentiated patients with IS from SMs with an area under the curve (AUC) of 0.90 in the replication sample, which was superior to multimodal cranial computed tomography (CT; AUC = 0.80) obtained for routine diagnostics. They were further superior to previously published

and tandem mass spectrometry. Participants with depressive symptoms had lower neuroactive steroids (dehydroepiandrosterone sulfate [DHEA-S], androstenediols, and pregnenolone sulfate) compared with those without depressive symptoms. The cortisol/DHEA-S ratio, an indicator of hypothalamic-pituitary-adrenal axis imbalance, was associated with depressive symptoms (P < .01) because of low DHEA-S levels

as the cause of DEE in eight probands, but the functional consequences of the mutations remained elusive. Here we demonstrate that both mutations (V990M and P1090Q) have distinct effects on TRPM3 gating, including increased basal activity, higher sensitivity to stimulation by the endogenous neurosteroid pregnenolone sulfate (PS) and heat, and altered response to ligand modulation. Most strikingly, the V990M

Disease-associated mutations in the human TRPM3 render the channel overactive via two distinct mechanisms. Transient Receptor Potential Melastatin 3 (TRPM3) is a Ca permeable non-selective cation channel activated by heat and chemical agonists such as pregnenolone sulfate and CIM0216. TRPM3 mutations in humans were recently reported to be associated with intellectual disability and epilepsy

Activation of the cation channel TRPM3 in perivascular nerves induces vasodilation of resistance arteries. The Transient Receptor Potential Melastatin 3 (TRPM3) is a Ca-permeable non-selective cation channel activated by the neurosteroid pregnenolone sulfate (PS). This compound was previously shown to contract mouse aorta by activating TRPM3 in vascular smooth muscle cells (VSMC), and proposed

disorders. Some evidence suggests that TPA-023, (7-(1,1-dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b] pyridazine), a GABA α2,3 subtype-selective GABA partial agonist and α antagonist, and the neurosteroid, pregnenolone sulfate, a GABA antagonist, may improve CIAS in pilot clinical trials. The goal of this study was to investigate the effect of TPA-023

, the women with PE and SGA had significantly higher levels of 20α-dihydroprogesterone (20α-DHP) and 20α-DHP/progesterone ratios. Pregnenolone sulfate levels were lower in the PE group than in the NP and SGA groups. Decreased expression of aromatase was observed in the PE group compared to the control group. Preeclampsia appears to be characterized by specific steroidogenesis dysregulation long before PE