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Pregnenolone

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https://www.readbyqxmd.com/read/29030154/simultaneous-profiles-of-sulfonated-androgens-sulfonated-estrogens-and-sulfonated-progestogens-in-postpubertal-boars-sus-scrofa-domestica-measured-by-lc-ms-ms
#1
G Schuler, A Sánchez-Guijo, M F Hartmann, S A Wudy
Sulfonated steroids (s-St) have been usually regarded as inactive metabolites but are progressively considered as precursors for the intra-tissue formation of bioactive steroids. Moreover, independent effects without preceding removal of the sulfate group have been observed. We use the porcine testicular-epididymal compartment as a model to investigate the still largely unknown s-St physiology as the boar exhibits an intriguingly broad s-St spectrum predominantly originating from the testis. The application of LC-MS/MS in steroidomics enables the determination of unconjugated and intact sulfonated steroids with currently highest specificity and good sensitivity, allowing the concurrent measuring of numerous analytes in larger quantities of samples...
October 10, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28991453/active-site-structures-of-cyp11a1-in-the-presence-of-its-physiological-substrates-and-alterations-upon-binding-of-adrenodoxin
#2
Qianhong Zhu, Piotr Mak, Robert C Tuckey, James R Kincaid
The rate limiting step in the steroid synthesis pathway is catalyzed by CYP11A1 through three sequential reactions. The first two steps involve hydroxylations at the 22- and 20- positions, generating 20R,22R-dihydroxycholesterol (20R,22R-DiOHCH), with the third stage leading to a C20-C22 bond cleavage, forming pregnenolone. The present work provides detailed information on active site structure of CYP11A1 in the resting state and substrate-bound ferric forms as well as the CO-ligated adducts. In addition, high quality resonance Raman spectra are reported for the dioxygen complexes, providing new insight into the status of Fe-O-O fragments encountered in the enzymatic cycle...
October 9, 2017: Biochemistry
https://www.readbyqxmd.com/read/28982580/stimulation-of-transient-receptor-potential-m3-trpm3-channels-increases-interleukin-8-gene-promoter-activity-involving-ap-1-and-extracellular-signal-regulated-protein-kinase
#3
Sandra Rubil, Andrea Lesch, Naofumi Mukaida, Gerald Thiel
Stimulation of Ca(2+) permeable TRPM3 (transient receptor potential melastatin-3) channels with the steroid ligand pregnenolone sulfate activates stimulus-responsive transcription factors, including the transcription factor AP-1 (activator protein-1). As part of a search for AP-1-regulated target genes we analyzed the gene encoding interleukin-8 (IL-8) in HEK293 cells expressing TRPM3 channels. Here, we show that stimulation of TRPM3 channels activated transcription of an IL-8 promoter-controlled reporter gene that was embedded into the chromatin of the cells...
October 2, 2017: Cytokine
https://www.readbyqxmd.com/read/28971759/steroidal-oximes-useful-compounds-with-antitumor-activities
#4
Catarina Canário, Samuel Silvestre, Amílcar Falcão, Gilberto Alves
BACKGROUND: Steroids play an important role in life because they can regulate a variety of biological processes and have been widely used in medicine namely as anti-inflammatory, anabolic, contraceptives and anticancer drugs. In recent years, there has been an increasing interest in the introduction of the oxime group in a large variety of molecules in order to increase their biological effects. This review highlights steroidal oximes with anticancer properties and their potential mechanisms of action, as well as data on their relative potencies reported in literature in the last few years...
October 3, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28951227/transport-of-steroid-3-sulfates-and-steroid-17-sulfates-by-the-sodium-dependent-organic-anion-transporter-soat-slc10a6
#5
Gary Grosser, Josefine Bennien, Alberto Sánchez-Guijo, Katharina Bakhaus, Barbara Döring, Michaela Hartmann, Stefan A Wudy, Joachim Geyer
The sodium-dependent organic anion transporter SOAT/Soat shows highly specific transport activity for sulfated steroids. SOAT substrates identified so far include dehydroepiandrosterone sulfate, 16α-hydroxydehydroepiandrosterone sulfate, estrone-3-sulfate, pregnenolone sulfate, 17β-estradiol-3-sulfate, and androstenediol sulfate. Apart from these compounds, many other sulfated steroids occur in mammals. Therefore, we aimed to expand the substrate spectrum of SOAT and analyzed the SOAT-mediated transport of eight different sulfated steroids by combining in vitro transport experiments in SOAT-transfected HEK293 cells with LC-MS/MS analytics of cell lysates...
September 23, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28951168/ziram-inhibits-aromatase-activity-in-human-placenta-and-jeg-3-cell-line
#6
Lanlan Chen, Xiaomin Chen, Xiaozhen Chen, Zhiyan Hu, Xiaoheng Li, Ying Su, Xingwang Li, Ren-Shan Ge
Placenta produces progesterone and estradiol for maintaining pregnancy. Two critical enzymes are responsible for their production: 3β-hydroxysteroid dehydrogenase 1 (HSD3B1) that catalyzes the formation of progesterone from pregnenolone and aromatase that catalyzes the production of estradiol from testosterone. Fungicide ziram may disrupt the placental steroid production. In the present study, we investigated the effects of ziram on steroid formation in human placental cell line JEG-3 cells and on HSD3B1 and aromatase in the human placenta...
September 23, 2017: Steroids
https://www.readbyqxmd.com/read/28948822/changes-to-fetal-steroidogenesis-caused-by-maternal-smoking
#7
K Adamcová, L Kolátorová, T Chlupáčová, M Šimková, H Jandíková, A Pařízek, L Stárka, M Dušková
Smoking during pregnancy presents health risks for both the mother and her child. In this study we followed changes in the production of steroid hormones in pregnant smokers. We focused on changes in steroidogenesis in the blood of mothers in their 37(th) week of pregnancy and in mixed cord blood from their newborns. The study included 88 healthy women with physiological pregnancies (17 active smokers and 71 non-smokers). We separately analyzed hormonal changes associated with smoking according to the sex of newborns...
September 26, 2017: Physiological Research
https://www.readbyqxmd.com/read/28948821/sex-differences-in-the-effect-of-prenatal-testosterone-exposure-on-steroid-hormone-production-in-adult-rats
#8
E Domonkos, V Borbélyová, L Kolátorová, T Chlupáčová, D Ostatníková, J Hodosy, L Stárka, P Celec
Maternal hyperandrogenism during pregnancy might have metabolic and endocrine consequences on the offspring as shown for the polycystic ovary syndrome. Despite numerous experiments, the impact of prenatal hyperandrogenic environment on postnatal sex steroid milieu is not yet clear. In this study, we investigated the effect of prenatal testosterone excess on postnatal concentrations of luteinizing hormone, corticosterone and steroid hormones including testosterone, pregnenolone, progesterone, estradiol and 7beta-hydroxy-epiandrosterone in the offspring of both sexes...
September 26, 2017: Physiological Research
https://www.readbyqxmd.com/read/28944830/application-of-the-amniotic-fluid-metabolome-to-the-study-of-fetal-malformations-using-down-syndrome-as-a-specific-model
#9
Jun Huang, Jinhua Mo, Guili Zhao, Qiyin Lin, Guanhui Wei, Weinan Deng, Dunjin Chen, Bolan Yu
Although monitoring and diagnosis of fetal diseases in utero remains a challenge, metabolomics may provide an additional tool to study the etiology and pathophysiology of fetal diseases at a functional level. In order to explore specific markers of fetal disease, metabolites were analyzed in two separate sets of experiments using amniotic fluid from fetuses with Down syndrome (DS) as a model. Both sets included 10‑15 pairs of controls and cases, and amniotic fluid samples were processed separately; metabolomic fingerprinting was then conducted using UPLC‑MS...
September 18, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28919340/design-and-synthesis-of-pregnenolone-2-cyanoacryloyl-conjugates-with-dual-nf-%C3%AE%C2%BAb-inhibitory-and-anti-proliferative-activities
#10
Jia-Li Song, Juan Zhang, Chang-Liang Liu, Chao Liu, Kong-Kai Zhu, Fei-Fei Yang, Xi-Gong Liu, João Paulo Figueiró Longo, Luis Alexandre Muehlmann, Ricardo Bentes Azevedo, Yu-Ying Zhang, Yue-Wei Guo, Cheng-Shi Jiang, Hua Zhang
Twenty-five novel pregnenolone/2-cyanoacryloyl conjugates (6-30) were designed and prepared, with the aim of developing novel anticancer drugs with dual NF-κB inhibitory and anti-proliferative activities. Compounds 22 and 27-30 showed inhibition against TNF-α-induced NF-κB activation in luciferase assay, which was confirmed by Western blotting. Among them, compound 30 showed potent NF-κB inhibitory activity (IC50=2.5μM) and anti-proliferative against MCF-7, A549, H157, and HL-60 cell lines (IC50=6.5-36...
September 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28918287/steroid-hormones-and-persistent-organic-pollutants-in-plasma-from-north-eastern-atlantic-pilot-whales
#11
Katrin S Hoydal, Bjarne Styrishave, Tomasz M Ciesielski, Robert J Letcher, Maria Dam, Bjørn M Jenssen
Persistent organic pollutants (POPs) are known to have endocrine disruptive effects, interfering with endogenous steroid hormones. The present study examined nine steroid hormones and their relationships with the concentrations of selected POPs in pilot whales (Globicephala melas) from the Faroe Islands, NE Atlantic. The different steroids were detected in 15 to all of the 26 individuals. High concentrations of progesterone (83.3-211.7pmol/g) and pregnenolone (PRE; 4.68-5.69pmol/g) were found in three adult females indicating that they were pregnant or ovulating...
November 2017: Environmental Research
https://www.readbyqxmd.com/read/28904054/a-13-steroid-serum-panel-based-on-lc-ms-ms-use-in-detection-of-adrenocortical-carcinoma
#12
David R Taylor, Lea Ghataore, Lewis Couchman, Royce P Vincent, Ben Whitelaw, Dylan Lewis, Salvador Diaz-Cano, Gabriele Galata, Klaus-Martin Schulte, Simon Aylwin, Norman F Taylor
BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignancy, with an annual incidence of 1 or 2 cases per million. Biochemical diagnosis is challenging because up to two-thirds of the carcinomas are biochemically silent, resulting from de facto enzyme deficiencies in steroid hormone biosynthesis. Urine steroid profiling by GC-MS is an effective diagnostic test for ACC because of its capacity to detect and quantify the increased metabolites of steroid pathway synthetic intermediates...
September 13, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28893621/rare-genetic-variants-in-the-sodium-dependent-organic-anion-transporter-soat-slc10a6-effects-on-transport-function-and-membrane-expression
#13
Josefine Bennien, Thomas Fischer, Joachim Geyer
Sulfo-conjugated steroid hormones, such as dehydroepiandrosterone sulfate (DHEAS), pregnenolone sulfate or estrone-3-sulfate are abundant in the body, but are biologically inactive at classical androgen and estrogen steroid receptors. However, after carrier-mediated import and de-conjugation by the steroid sulfatase, these compounds participate in the overall steroid regulation of reproductive organs. The sodium-dependent organic anion transporter SOAT, coded by the SLC10A6 gene, is specific for the transport of steroid sulfates and is highly expressed in testicular germ cells, including pachytene spermatocytes, secondary spermatocytes, and round spermatids...
September 8, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28890368/cyp17a1-independent-production-of-the-neurosteroid-derived-5%C3%AE-pregnan-3%C3%AE-6%C3%AE-diol-20-one-in-androgen-responsive-prostate-cancer-cell-lines-under-serum-starvation-and-inhibition-by-abiraterone
#14
Antonio G Gomes de Mello Martins, Giuseppe Allegretta, Gerhard Unteregger, Jörg Haupenthal, Jens Eberhard, Michael Hoffmann, Jill A van der Zee, Kerstin Junker, Michael Stöckle, Rolf Müller, Rolf W Hartmann, Carsten-H Ohlmann
CYP17A1-independent intratumoral steroid hormone synthesis is regarded as one possible explanation for resistance to treatment with the CYP17-inhibitor Abiraterone (Abi). The aim of our study was therefore to investigate the steroid metabolism of prostate cancer cells under serum starvation and the effects of Abi treatment. We assessed steroid metabolism in a panel of prostate cancer cells under serum starvation by radioactivity detector-coupled HPLC and HPLC-ESI-ToF-mass spectrometry after treatment with pregnenolone, progesterone and allopregnanolone...
September 7, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28878092/equine-fetal-adrenal-gonadal-and-placental-steroidogenesis
#15
Erin L Legacki, Barry A Ball, C Jo Corbin, Shavahn C Loux, Kirsten E Scoggin, Scott D Stanley, Alan J Conley
Equine fetuses have substantial circulating pregnenolone concentrations and thus have been postulated to provide significant substrate for placental 5α-reduced pregnane production, but the fetal site of pregnenolone synthesis remains unclear. The current studies investigated steroid concentrations in blood, adrenal glands, gonads and placenta from fetuses (4, 6, 9 and 10 months of gestational age (GA)), as well as tissue steroidogenic enzyme transcript levels. Pregnenolone and dehydroepiandrosterone (DHEA) were the most abundant steroids in fetal blood, pregnenolone was consistently higher but decreased progressively with GA...
October 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28831034/stimulatory-effect-of-intermittent-hypoxia-on-the-production-of-corticosterone-by-zona-fasciculata-reticularis-cells-in-rats
#16
Guey-Shyang Hwang, Chih-Chieh Chen, Jou-Chun Chou, Ling-Ling Chang, Shu-Fen Kan, Wei-Ho Lai, Fu-Kong Lieu, Sindy Hu, Paulus S Wang, Shyi-Wu Wang
Hypoxia or intermittent hypoxia (IH) have known to alter both synthesis and secretion of hormones. However, the effect of IH on the production of adrenal cortical steroid hormones is still unclear. The aim of present study was to explore the mechanism involved in the effect of IH on the production of corticosterone by rat ZFR cells. Male rats were exposed at 12% O2 and 88% N2 (8 hours per day) for 1, 2, or 4 days. The ZFR cells were incubated at 37 °C for 1 hour with or without ACTH, 8-Br-cAMP, calcium ion channel blockers, or steroidogenic precursors...
August 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28829742/inhibition-of-transient-receptor-potential-melastatin-3-ion-channels-by-g-protein-%C3%AE-%C3%AE-subunits
#17
Doreen Badheka, Yevgen Yudin, Istvan Borbiro, Cassandra M Hartle, Aysenur Yazici, Tooraj Mirshahi, Tibor Rohacs
Transient receptor potential melastatin 3 (TRPM3) channels are activated by heat, and chemical ligands such as pregnenolone sulphate (PregS) and CIM0216. Here, we show that activation of receptors coupled to heterotrimeric Gi/o proteins inhibits TRPM3 channels. This inhibition was alleviated by co-expression of proteins that bind the βγ subunits of heterotrimeric G-proteins (Gβγ). Co-expression of Gβγ, but not constitutively active Gαi or Gαo, inhibited TRPM3 currents. TRPM3 co-immunoprecipitated with Gβ, and purified Gβγ proteins applied to excised inside-out patches inhibited TRPM3 currents, indicating a direct effect...
August 15, 2017: ELife
https://www.readbyqxmd.com/read/28825834/combining-genomics-to-identify-the-pathways-of-post-transcriptional-nongenotoxic-signaling-and-energy-homeostasis-in-livers-of-rats-treated-with-the-pregnane-x-receptor-agonist-pregnenolone-carbonitrile
#18
Hirohisa Nagahori, Kenji Nakamura, Kayo Sumida, Shingo Ito, Sumio Ohtsuki
Transcriptomic, proteomic, phosphoproteomic, and metabolomic analyses were combined to determine the role of pregnane X receptor (PXR) in nongenotoxic signaling and energy homeostasis in liver after rats were repeatedly orally dosed with the PXR agonist pregnenolone carbonitrile (PCN) for 7 days. Analyses of mRNAs and proteins in the supernatant, membrane, and cytosolic fractions of enlarged liver homogenates showed diverse expression profiles. Gene set enrichment analysis showed that the synchronous increase in mRNAs and proteins involved in chemical carcinogenesis and the response to drug was possibly mediated by the PXR pathway and proteasome core complex assembly was possibly mediated by the Nrf2 pathway...
September 6, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28825678/effects-of-refined-xiaoyaosan-on-depressive-like-behaviors-in-rats-with-chronic-unpredictable-mild-stress-through-neurosteroids-their-synthesis-and-metabolic-enzymes
#19
Xiaoling Guo, Wenqi Qiu, Yueyun Liu, Yifang Zhang, Hongbo Zhao, Jiaxu Chen
Abstract: To observe the effects of refined Xiaoyaosan (XYS) on the depressive-like behaviors in rats with chronic unpredictable mild stress (CUMS), and to explore the relationship between the changes of neurosteroids and mRNA expressions of their synthesis and metabolic enzymes, and the mechanism of XYS in the treatment of depression. Methods: Eighty-four healthy male Sprague-Dawley rats were randomly divided into normal group, model group, XYS group and fluoxetine group. The latter three groups were subjected to 21 days of CUMS to prepare the stress depression model...
August 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28803965/the-great-divide-separation-between-in%C3%A2-vitro-and-in%C3%A2-vivo-effects-of-psncbam-based-cb1-receptor-allosteric-modulators
#20
Thomas F Gamage, Charlotte E Farquhar, Timothy W Lefever, Brian F Thomas, Thuy Nguyen, Yanan Zhang, Jenny L Wiley
While allosteric modulators of the cannabinoid type-1 receptor (CB1) continue to be developed and characterized, the gap between the in vitro and in vivo data is widening, raising questions regarding translatability of their effects and biological relevance. Among the CB1 allosteric modulators, PSNCBAM-1 has received little attention regarding its effects in vivo. Recently, pregnenolone was reported to act as an allosteric modulator of CB1, blocking THC's effects in vitro and in vivo, highlighting the potential of CB1 allosteric modulators for treatment of cannabis intoxication...
August 10, 2017: Neuropharmacology
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