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Pregnenolone

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https://www.readbyqxmd.com/read/28213302/disrupting-effects-of-azocyclotin-to-the-hypothalamo-pituitary-gonadal-axis-and-reproduction-of-xenopus-laevis
#1
Shuying Li, Meng Li, Wenjun Gui, Qiangwei Wang, Guonian Zhu
Over the past few decades, the hazards associated with the extensive use of organictin compounds have become an issue of extreme concern, while at present the effects of these substances on amphibians remain poorly understood. In the present study, we chose azocyclotin, one of common use acaricides in China. We focused on sexual development and steroidogenesis disrupting effects of azocyclotin in the Xenopus laevis. Tadpoles were exposed to azocyclotin (0.05 and 0.5μg/L) for long-term (4 months) study. Results showed that exposure to azocyclotin caused developmental toxicity, including decreased survival, body weight, body length, gonadosomatic index, hepatosomatic index and female phenotype...
February 8, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28205173/measurement-of-mitochondrial-cholesterol-import-using-a-mitochondria-targeted-cyp11a1-fusion-construct
#2
Barry E Kennedy, Mark Charman, Barbara Karten
All animal membranes require cholesterol as an essential regulator of biophysical properties and function, but the levels of cholesterol vary widely among different subcellular compartments. Mitochondria, and in particular the inner mitochondrial membrane, have the lowest levels of cholesterol in the cell. Nevertheless, mitochondria need cholesterol for membrane maintenance and biogenesis, as well as oxysterol, steroid, and hepatic bile acid production. Alterations in mitochondrial cholesterol have been associated with a range of pathological conditions, including cancer, hepatosteatosis, cardiac ischemia, Alzheimer's, and Niemann-Pick Type C Disease...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28202325/synthesis-and-biological-evaluation-of-heterocyclic-analogues-of-pregnenolone-as-novel-anti-osteoporotic-agents
#3
Saransh Wales Maurya, Kapil Dev, Krishna Bhan Singh, Reena Rai, Ibadur Rahman Siddiqui, Divya Singh, Rakesh Maurya
The structural modifications of pregnenolone have been described via the introduction of heterocyclic moieties at C-17 position by limiting the acyl group. Novel heterocyclic analogues of pregnenolone have been synthesized by using Friedlander and Claisen-Schmidt reactions, and the synthesized compounds were evaluated for their osteogenic activity. Among the synthesized derivatives, four compounds showed significantly increased ALP activity. Among all four active compounds, the novel compound 3a has shown significant bone matrix mineralization and mRNA expressions of osteogenic marker genes, BMP2, RUNX-2 and OCN at 1pM concentration...
February 4, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28129443/anxiolytic-effects-of-hippocampal-neurosteroids-in-normal-and-neuropathic-rats-with-spared-nerve-injury
#4
Meng Zhang, Jia Liu, Meng-Meng Zhou, Honghai Wu, Yanning Hou, Yun-Feng Li, Yuxin Yin, Lemin Zheng, Jie Cai, Fei-Fei Liao, Feng-Yu Liu, Ming Yi, You Wan
Neurosteroids are synthesized in the nervous system from cholesterol or steroidal precursors imported from peripheral sources. These compounds are important allosteric modulators of GABAA receptors, which play a vital role in modulating hippocampal functions. Chronic pain is accompanied by increased neurosteroid production in the spinal cord and thalamus. We hypothesize that hippocampal neurosteroids participate in pain or pain-associated emotions, which we tested with high-performance liquid chromatography/tandem mass spectrometry and pharmacological behavioral tests...
January 27, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28115639/combined-effects-of-gestational-phthalate-exposure-and-zinc-deficiency-on-steroid-metabolism-and-growth
#5
J Nuttall, H R Kucera, S Supasai, N W Gaikwad, P I Oteiza
Disruption of steroid hormone signaling has been implicated independently in the developmental abnormalities resulting from maternal phthalate plasticizer exposure and developmental zinc deficiency. This study investigated if secondary zinc deficiency may result from dietary exposure to a low level of DEHP through gestation and if this could be associated with altered steroid metabolism. The interaction between marginal zinc nutrition and DEHP exposure to affect pregnancy outcome, zinc status, and steroid metabolism was also assessed...
January 23, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28114089/-non-conventional-pharmacological-agents-for-the-treatment-of-bipolar-disorder-%C3%AE-systematic-review-of-the-evidence
#6
K N Fountoulakis, D Balaris, V Nikolaou, J Νimatoudis
Bipolar disorder (BD) has a complex and variable clinical picture which is characterized by many different phacets and phases and as a result its therapeutical options are also complex and often unsatisfactory. Typically the so-called "mood stabilizers" are used in the treatment of BD and in this class lithium and specific antiepileptics are included. The present study aimed to systematically review the literature concerning the presence of randomized double blind clinical trials of 'non conventional' pharmaceutical treatment options...
October 2016: Psychiatrikē, Psychiatriki
https://www.readbyqxmd.com/read/28112420/extracellular-signal-regulated-protein-kinase-c-jun-n-terminal-protein-kinase-and-calcineurin-regulate-transient-receptor-potential-m3-trpm3-induced-activation-of-ap-1
#7
Andrea Lesch, Oliver G Rössler, Gerald Thiel
Stimulation of transient receptor potential M3 (TRPM3) cation channels with pregnenolone sulfate induces an influx of Ca(2+) ions into the cells and a rise in the intracellular Ca(2+) concentration, leading to the activation of the activator protein-1 (AP-1) transcription factor. Here, we show that expression of a constitutively active mutant of the Ca(2+) /calmodulin-dependent protein phosphatase calcineurin attenuated pregnenolone sulfate-induced AP-1 activation in TRPM3-expressing cells. Likewise, expression of the regulatory B subunit of calcineurin reduced AP-1 activity in the cells following stimulation of TRPM3 channels...
January 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28110963/hyperforin-activates-gene-transcription-involving-transient-receptor-potential-c6-channels
#8
Gerald Thiel, Oliver G Rössler
Hypericum perforatum is one of the most prominent medical plants. Hyperforin, a main ingredient of H. perforatum, has been shown to activate transient receptor potential canonical C6 (TRPC6) channels. Alternatively, it has been proposed that hyperforin functions as a protonophore in a TRPC6-independent manner. Here, we show that hyperforin stimulation activates the transcription factor AP-1 in HEK293 cells expressing TRPC6 (T6.11 cells), but did not substantially change the AP-1 activity in HEK293 cells lacking TRPC6...
January 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28106668/primidone-inhibits-trpm3-and-attenuates-thermal-nociception-in-vivo
#9
Ute Krügel, Isabelle Straub, Holger Beckmann, Michael Schaefer
The melastatin-related transient receptor potential channel TRPM3 is a nonselective cation channel expressed in nociceptive neurons and activated by heat. Since TRPM3-deficient mice show inflammatory thermal hyperalgesia, pharmacological inhibition of TRPM3 may exert antinociceptive properties. Fluorometric Ca influx assays and a compound library containing approved or clinically tested drugs were used to identify TRPM3 inhibitors. Biophysical properties of channel inhibition were assessed using electrophysiological methods...
January 12, 2017: Pain
https://www.readbyqxmd.com/read/28104494/thoughts-on-interactions-between-pgrmc1-and-diverse-attested-and-potential-hydrophobic-ligands
#10
REVIEW
Michael A Cahill, Amy E Medlock
Progesterone Receptor Membrane Component 1 (PGRMC1) is located in many different subcellular locations with many different attested and probably location-specific functions. PGRMC1 was recently identified in the mitochondrial outer membrane where it interacts with ferrochelatase, the last enzyme in the heme synthetic pathway. It has been proposed that PGRMC1 may act as a chaperone to shuttle newly synthesized heme from the mitochondrion to cytochrome P450 (cyP450) enzymes. Here we consider potential roles that PGRMC1 may play in transferring heme, and other small hydrophobic ligands such as cholesterol and steroids, between the hydrophobic compartment of the membrane lipid bilayer interior to aqueous proteins, and perhaps to the membranes of other organelles...
January 16, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28102853/skin-to-skin-contact-after-birth-and-the-natural-course-of-neurosteroid-levels-in-healthy-term-newborns
#11
K R McCallie, N W Gaikwad, M E Castillo Cuadrado, M Aleman, J E Madigan, D K Stevenson, V K Bhutani
OBJECTIVE: To determine the postnatal course of neurosteroid levels in relation to gender, mode of delivery and the extent of skin-to-skin (STS) contact during the first days of life in healthy term newborns. STUDY DESIGN: Prospective observational study of 39 neonates in which parents recorded total duration of STS in the first 2 days and nine neurosteroids (dehydroepiandrosterone-sulfate, progesterone, pregnenolone, pregnenolone-sulfate, allopregnanolone, isopregnanolone, epipregnanolone, pregnanolone and pregnanolone-sulfate) were assayed from blood samples at birth and at 1-2 days of age...
January 19, 2017: Journal of Perinatology: Official Journal of the California Perinatal Association
https://www.readbyqxmd.com/read/28091906/effect-of-mifepristone-on-corticosteroid-production-in-vitro-by-adrenal-glands-of-rats-with-streptozotocin-diabetes
#12
N V Kuznetsova, N A Palchikova, V G Selyatitskaya, O I Kuzminova
Changes in pregnenolone and corticosterone production by the adrenal glands of normoglycemic rats receiving the course of intraperitoneal mifepristone or NaCl administration were co-directed, but differed in magnitude. In rats with hyperglycemia, corticosteroid production increased after NaCl administration over 5 days and returned to the initial values after 15-day administration. On the contrary, pregnenolone and corticosterone production was suppressed after 5-day course of mifepristone, but significantly increased after mifepristone administration for 15 days...
January 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27974436/genetic-and-targeted-eqtl-mapping-reveals-strong-candidate-genes-modulating-the-stress-response-during-chicken-domestication
#13
Amir Fallahsharoudi, Neil de Kock, Martin Johnsson, Lejla Bektic, S J Kumari A Ubhayasekera, Jonas Bergquist, Dominic Wright, Per Jensen
The stress response has been largely modified in all domesticated animals, offering a strong tool for genetic mapping. In chickens, ancestral Red Junglefowl react stronger both in terms of physiology and behavior to a brief restraint stress than domesticated White Leghorn, demonstrating modified functions of the hypothalamic-pituitary-adrenal (HPA) axis. We mapped quantitative trait loci (QTL) underlying variations in stress induced hormone levels using 232 birds from the 12th generation of an advanced intercross between White Leghorn and Red Junglefowl, genotyped for 739 genetic markers...
December 14, 2016: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/27934105/simultaneous-analysis-of-free-and-sulfated-steroids-by-liquid-chromatography-mass-spectrometry-with-selective-mass-spectrometric-scan-modes-and-polarity-switching
#14
Su Hyeon Lee, Nanhee Lee, Youngmin Hong, Bong Chul Chung, Man Ho Choi
Sulfated steroids can act as a latent form of active free steroids, coexisting with them in biological specimens. To evaluate the metabolic significance of free and sulfated steroid species, a simultaneous analysis of eight free steroids [cholesterol, pregnenolone, 17α-hydroxypregnenolone, progesterone, 17α-hydroxyprogesterone, dehydroepiandrosterone (DHEA), testosterone, and 17β-estradiol] and four biologically relevant sulfated steroids was developed and validated, using selected-ion and multiple-reaction monitoring modes coupled to polarity-switching liquid chromatography/mass spectrometry (LC/MS)...
December 6, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27917709/synthesis-of-some-steroidal-derivatives-with-side-chain-of-20-and-22-hydrazone-aromatic-heterocycles-and-their-antiproliferative-acitivity
#15
Chunfang Gan, Liang Liu, Jianguo Cui, Zhiping Liu, Haixin Shi, Qifu Lin, Haibing Sheng, Chunhui Yang, Yanmin Huang
BACKGROUND: The modification of steroidal structure is commonly used to change the biological activity of steroids in medicinal chemistry. Some steroids containing heterocycles exhibit distinct cytotoxicity against various cancer cell lines and have been gotten wide attention over the years by medicinal chemists for drug discovery. METHODS: Using pregnenolone and stigmasterol as starting materials, via different chemical reaction, two series of heterosteroids with side chain of 20- and 22-hydrazone aromatic cycles or heterocycles in their structures were synthesized and characterized by IR, NMR and HRMS...
December 5, 2016: Medicinal Chemistry
https://www.readbyqxmd.com/read/27914864/serum-dhea-s-concentration-correlates-with-clinical-symptoms-and-neurocognitive-function-in-patients-with-bipolar-ii-disorder-a-case-controlled-study
#16
Sheng-Yu Lee, Liang-Jen Wang, Cheng-Ho Chang, Chih-Ching Wu, Hsing-Ling Chen, Shih-Hsien Lin, Chin-Liang Chu, Ti Lu, Ru-Band Lu
OBJECTIVES: Dysregulation of the neuroendocrine system including dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and pregnenolone may play a role in the pathophysiology of bipolar II disorder (BP-II). The aims of the current study are to determine (a) the differences in DHEA, DHEA-S and pregnenolone in patients with BP-II and controls; and (b) the correlation of levels of the above hormones, cognitive function, and clinical symptoms. METHODS: Patients diagnosed with BP-II and healthy controls were recruited from psychiatric department...
March 6, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/27913096/a-sensitive-and-accurate-lc-ms-ms-assay-with-the-derivatization-of-1-amino-4-methylpiperazine-applied-to-serum-allopregnanolone-pregnenolone-and-androsterone-in-pre-and-postmenopausal-women
#17
Yuyong Ke, Renaud Gonthier, Fernand Labrie
The concentrations of allopregnanolone (Allopreg), pregnenolone (Preg) and androsterone (ADT) are very low in the circulation, especially in postmenopausal women, resulting in a considerable challenge for their accurate measurements in serum or plasma. In this report, a sensitive and reliable LC-MS/MS assay method has been developed using a simple sample preparation and the 1-Amino-4-methylpiperazine (AMP) derivatization procedure. A 5pg/ml (0.1pg on column) of low limit of quantitation has been achieved for Allopreg, Preg and ADT, with a sensitivity comparable to data obtained with the commercial reagent...
November 29, 2016: Steroids
https://www.readbyqxmd.com/read/27890531/short-term-effects-of-diabetes-on-neurosteroidogenesis-in-the-rat-hippocampus
#18
Simone Romano, Nico Mitro, Silvia Diviccaro, Roberto Spezzano, Matteo Audano, Luis Miguel Garcia-Segura, Donatella Caruso, Roberto Cosimo Melcangi
Diabetes may induce neurophysiological and structural changes in the central nervous system (i.e., diabetic encephalopathy). We here explored whether the levels of neuroactive steroids (i.e., neuroprotective agents) in the hippocampus may be altered by short-term diabetes (i.e., one month). To this aim, by liquid chromatography-tandem mass spectrometry we observed that in the experimental model of the rat raised diabetic by streptozotocin injection, one month of pathology induced changes in the levels of several neuroactive steroids, such as pregnenolone, progesterone and its metabolites (i...
March 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27888513/decreased-allopregnanolone-levels-in-cerebrospinal-fluid-obtained-during-status-epilepticus
#19
Stefano Meletti, Chiara Lucchi, Giulia Monti, Giada Giovannini, Roberta Bedin, Tommaso Trenti, Cecilia Rustichelli, Giuseppe Biagini
Neuroactive steroids are increasingly considered as relevant modulators of neuronal activity. Especially allopregnanolone (AP) and pregnenolone sulfate (PS) have been shown to possess, respectively, anticonvulsant or proconvulsant properties. In view of the potential role of these steroids, we aimed at evaluating AP and PS levels in cerebrospinal fluid (CSF) and blood samples obtained from patients with status epilepticus (SE). To this purpose, we enrolled 41 patients affected by SE and 41 subjects investigated for nonepileptic neurologic disorders...
November 26, 2016: Epilepsia
https://www.readbyqxmd.com/read/27884493/initial-genetic-dissection-of-serum-neuroactive-steroids-following-chronic-intermittent-ethanol-across-bxd-mouse-strains
#20
Patrizia Porcu, Todd K O'Buckley, Marcelo F Lopez, Howard C Becker, Michael F Miles, Robert W Williams, A Leslie Morrow
Neuroactive steroids modulate alcohol's impact on brain function and behavior. Ethanol exposure alters neuroactive steroid levels in rats, humans, and some mouse strains. We conducted an exploratory analysis of the neuroactive steroids (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP), (3α,5α)-3,21-dihydroxypregnan-20-one (3α,5α-THDOC), and pregnenolone across 126-158 individuals and 19 fully inbred strains belonging to the BXD family, which were subjected to air exposure, or chronic intermittent ethanol (CIE) exposure...
February 2017: Alcohol
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