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https://www.readbyqxmd.com/read/29680774/targeting-hypothalamic-pituitary-adrenal-axis-hormones-and-sex-steroids-for-improving-cognition-in-major-mood-disorders-and-schizophrenia-a-systematic-review-and-narrative-synthesis
#1
REVIEW
Virginia Soria, Alexandre González-Rodríguez, Elena Huerta-Ramos, Judith Usall, Jesús Cobo, Miquel Bioque, Juan David Barbero, Clemente García-Rizo, Meritxell Tost, José Antonio Monreal, Javier Labad
Cognitive deficits are a core feature of serious mental illnesses such as schizophrenia, major depressive disorder (MDD) and bipolar disorder (BD) and are a common cause of functional disability. There is limited efficacy of pharmacological interventions for improving the cognitive deficits in these disorders. As pro-cognitive pharmacological treatments are lacking, hormones or drugs that target the endocrine system may become potential candidates for 'repurposing' trials aiming to improve cognition. We aimed to study whether treatment with drugs targeting the hypothalamic-pituitary-adrenal (HPA) axis and sex steroids can improve cognition in patients with schizophrenia, MDD or BD...
April 14, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29671343/effects-of-genetic-polymorphisms-on-the-sulfation-of-dehydroepiandrosterone-and-pregnenolone-by-human-cytosolic-sulfotransferase-sult2a1
#2
Maryam S Abunnaja, Fatemah A Alherz, Amal A El Daibani, Ahsan F Bairam, Mohammed Ibrahim Rasool, Saud A Gohal, Katsuhisa Kurogi, Yoichi Sakakibara, Masahito Suiko, Ming-Cheh Liu
The cytosolic sulfotransferase (SULT) SULT2A1 is known to mediate the sulfation of dehydroepiandrosterone (DHEA) as well as some other hydroxysteroids such as pregnenolone. The present study was designed to investigate how genetic polymorphisms of the human SULT2A1 gene may affect the sulfation of DHEA and pregnenolone. Online databases were systematically searched to identify human SULT2A1 single nucleotide polymorphisms (SNPs). Of the 98 SULT2A1 non-synonymous coding SNPs identified, seven were selected for further investigation...
April 19, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29588428/expression-of-sult2a1-sult2b1-and-hsd3b1-in-the-porcine-testis-and-epididymis
#3
Bettina Zimmer, Linda Tenbusch, Michele C Klymiuk, Yaser Dezhkam, Gerhard Schuler
In the porcine testis in addition to estrogen sulfates the formation of numerous sulfonated neutral hydroxysteroids has been observed. However, their functions and the underlying synthetic pathways are still widely unclear. To obtain further information on their formation in postpubertal boars the expression of sulfotransferases considered relevant for neutral hydroxysteroids (SULT2A1, SULT2B1) was investigated in the testis and defined segments of the epididymis applying real-time RT-qPCR, Western blot and immunohistochemistry (IHC)...
March 27, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29568275/neurosteroids-in-schizophrenia-pathogenic-and-therapeutic-implications
#4
REVIEW
HuaLin Cai, Ting Cao, Xiang Zhou, Jeffrey K Yao
Neurosteroids are a group of important endogenous molecules affecting many neural functions in the brain. Increasing evidence suggests a possible role of these neurosteroids in the pathology and symptomatology of schizophrenia (SZ) and other mental disorders. The aim of this review is to summarize the current knowledge about the neural functions of neurosteroids in the brain, and to evaluate the role of the key neurosteroids as candidate modulators in the etiology and therapeutics of SZ. The present paper provides a brief introduction of neurosteroid metabolism and distribution, followed by a discussion of the mechanisms underlying neurosteroid actions in the brain...
2018: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/29566165/leydig-cells-formation-function-and-regulation
#5
Barry R Zirkin, Vassilios Papadopoulos
Herein we summarize important discoveries made over many years about Leydig cell function and regulation. During the fetal period, fetal Leydig cells produce the high levels of androgen (testosterone or androstenedione, depending upon the species) required for differentiation of male genitalia and brain masculinization. Androgen production declines with loss of these cells, reaching a nadir at postpartum. Testosterone then gradually increases to high levels with adult Leydig cell development from stem cells...
March 16, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29561593/an-isotope-dilution-based-targeted-and-non-targeted-carbonyl-neurosteroid-steroid-profiling
#6
Sheila Sharp, Scott J Mitchell, Monique Vallée, Elena Kuzmanova, Michelle Cooper, Delia Belelli, Jeremy J Lambert, Jeffrey T-J Huang
Neurosteroids are brain-derived steroids, capable of rapidly modulating neuronal excitability in a non-genomic manner. Dysregulation of their synthesis, or metabolism has been implicated in many pathological conditions. Here, we describe an isotope dilution based targeted and non-targeted (ID-TNT) profiling of carbonyl neurosteroids/steroids. The method combines stable isotope dilution, hydroxylamine derivatization, high-resolution MS scanning and data dependent MS/MS analysis, allowing absolute quantification of pregnenolone, progesterone, 5α-dihydroprogesterone, 3α,5α-tetrahydroprogesterone and 3β,5α-tetrahydroprogesterone, and relative quantification of other carbonyl containing steroids...
March 21, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29548889/comparison-of-the-hepatic-and-thyroid-gland-effects-of-sodium-phenobarbital-in-wild-type-and-constitutive-androstane-receptor-car-knockout-rats-and-pregnenolone-16%C3%AE-carbonitrile-in-wild-type-and-pregnane-x-receptor-pxr-knockout-rats
#7
Corinne Haines, Lynsey R Chatham, Audrey Vardy, Clifford R Elcombe, John R Foster, Brian G Lake
A number of chemicals produce liver and thyroid gland tumours in rodents by nongenotoxic modes of action (MOAs). In this study the hepatic and thyroid gland effects of the constitutive androstane receptor (CAR) activator sodium phenobarbital (NaPB) were examined in male Sprague-Dawley wild type (WT) rats and in CAR knockout (CAR KO) rats and the effects of the pregnane X receptor (PXR) activator pregnenolone-16α-carbonitrile (PCN) were examined in WT and PXR knockout (PXR KO) rats. Rats were either fed diets containing 0 (control) or 500 ppm NaPB or were dosed with 0 (control) or 100 mg/kg/day PCN orally for 7 days...
March 13, 2018: Toxicology
https://www.readbyqxmd.com/read/29502560/over-the-counter-adrenal-support-supplements-contain-thyroid-and-steroid-based-adrenal-hormones
#8
Halis Kaan Akturk, Ana Maria Chindris, Jolaine M Hines, Ravinder J Singh, Victor J Bernet
OBJECTIVE: To assess whether dietary supplements that are herbal and/or animal-derived products, marketed for enhancing metabolism or promoting energy, "adrenal fatigue," or "adrenal support," contain thyroid or steroid hormones. METHODS: Twelve dietary adrenal support supplements were purchased. Pregnenolone, androstenedione, 17-hydroxyprogesterone, cortisol, cortisone, dehydroepiandrosterone sulfate, synthetic glucocorticoids (betamethasone, dexamethasone, fludrocortisone, megestrol acetate, methylprednisolone, prednisolone, prednisone, budesonide, and triamcinolone acetonide) levels were measured twice in samples in a blinded fashion...
March 2018: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/29494825/gemfibrozil-and-carbamazepine-decrease-steroid-production-in-zebrafish-testes-danio-rerio
#9
Shamaila Fraz, Abigail H Lee, Joanna Y Wilson
Gemfibrozil (GEM) and carbamazepine (CBZ) are two environmentally relevant pharmaceuticals and chronic exposure of fish to these compounds has decreased androgen levels and fish reproduction in laboratory studies. The main focus of this study was to examine the effects of GEM and CBZ on testicular steroid production, using zebrafish as a model species. Chronic water borne exposures of adult zebrafish to 10 μg/L of GEM and CBZ were conducted and the dosing was confirmed by chemical analysis of water as 17...
February 10, 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29486070/expression-and-activity-profiling-of-the-steroidogenic-enzymes-of-glucocorticoid-biosynthesis-and-the-fdx1-co-factors-in-zebrafish
#10
Meltem Weger, Nicolas Diotel, Benjamin D Weger, Tanja Beil, Andreas Zaucker, Helen L Eachus, James A Oakes, Jean Luc do Rego, Karl-Heinz Storbeck, Philipp Gut, Uwe Straehle, Sepand Rastegar, Ferenc Mueller, Nils Krone
The spatial and temporal expression of steroidogenic genes in zebrafish has not been fully characterized. Since zebrafish are increasingly employed in endocrine and stress research, a better characterization of steroidogenic pathways is required to target specific steps in the biosynthetic pathways in the future. Here, we have systematically defined the temporal and spatial expression of steroidogenic enzymes involved in glucocorticoid biosynthesis (cyp21a2, cyp11c1, cyp11a1, cyp11a2, cyp17a1, cyp17a2, hsd3b1, hsd3b2), as well as the mitochondrial electron-providing co-factors ferredoxin (fdx1, fdx1b) during zebrafish development...
February 27, 2018: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/29455953/the-comprehensive-characterization-of-adrenocortical-steroidogenesis-using-two-dimensional-ultra-performance-liquid-chromatography-electrospray-ionization-tandem-mass-spectrometry
#11
Gellért Karvaly, Krisztián Kovács, Katalin Mészáros, Ibolya Kocsis, Attila Patócs, Barna Vásárhelyi
The perturbation of the homeostasis of adrenocortical steroids plays a fundamental role in several pathological conditions. Currently, only a few of the substances involved in steroidogenesis are routinely analysed in clinical laboratories for the diagnosis of these conditions. Recently, interest has grown over the development of clinical assays of endogenous steroids using liquid chromatography-tandem mass spectrometry (LC-MS/MS). However, no approaches have assessed the adrenocortical steroidogenesis comprehensively...
February 3, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29451725/selective-sp3-c-h-aerobic-oxidation-enabled-by-deca-tungstate-photocatalysis-in-flow
#12
Gabriele Laudadio, Sebastian Govaerts, Ying Wang, Davide Ravelli, Hannes Koolman, Maurizio Fagnoni, Stevan Djuric, Timothy Noel
A mild and selective sp3 C-H aerobic oxidation enabled by deca-tungstate photocatalysis has been developed. The reaction can be significantly improved in a microflow reactor enabling the safe use of oxygen and the enhanced irradiation of the reaction mixture. Our method allows for the oxidation of both activated and unactivated C-H bonds (30 examples). The ability to selectively oxidize natural scaffolds, such as (-)-ambroxide, pregnenolone acetate, (+)-sclareolide and artemisinin exemplifies the utility of this new method...
February 16, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29447845/probing-gaba-a-receptors-with-inhibitory-neurosteroids
#13
Sandra Seljeset, Damian P Bright, Philip Thomas, Trevor G Smart
γ-aminobutyric acid type A receptors (GABAA Rs) are important components of the central nervous system and they are functionally tasked with controlling neuronal excitability. These receptors are subject to post-translational modification and also to modulation by endogenous regulators, such as the neurosteroids. These modulators can either potentiate or inhibit GABAA R function. Whilst the former class of neurosteroids are considered to bind to and act from the transmembrane domain of the receptor, the domains that are important for the inhibitory neurosteroids remain less clear...
February 12, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29433072/pregnenolone-progesterone-allopregnanolone-pathway-as-a-potential-therapeutic-target-in-first-episode-antipsychotic-na%C3%A3-ve-patients-with-schizophrenia
#14
HuaLin Cai, Xiang Zhou, George G Dougherty, Ravinder D Reddy, Gretchen L Haas, Debra M Montrose, Matcheri Keshavan, Jeffrey K Yao
Neurosteroids are both endogenous and exogenous steroids that rapidly alter neuronal excitability through interactions with ligand-gated ion channels and other cell surface receptors. They are originated from cholesterol and have important implications for schizophrenia (SZ) pathophysiology and treatment strategies. Specifically, pregnenolone (PREG), progesterone (PROG) and allopregnanolone (ALLO) exhibit similar psychotropic properties. Using enzyme immunoassay, we compared the neurosteroids in PREG downstream pathways in plasma between healthy controls (HC, n = 43) and first-episode antipsychotic-naïve patients with SZ (FEAN-SZ, n = 53) before antipsychotic drug (APD) treatment...
February 7, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29429410/the-human-fetal-adrenal-produces-cortisol-but-no-detectable-aldosterone-throughout-the-second-trimester
#15
Zoe C Johnston, Michelle Bellingham, Panagiotis Filis, Ugo Soffientini, Denise Hough, Siladitya Bhattacharya, Marc Simard, Geoffrey L Hammond, Peter King, Peter J O'Shaughnessy, Paul A Fowler
BACKGROUND: Human fetal adrenal glands are highly active and, with the placenta, regulate circulating progesterone, estrogen and corticosteroids in the fetus. At birth the adrenals are essential for neonate salt retention through secretion of aldosterone, while adequate glucocorticoids are required to prevent adrenal insufficiency. The objective of this study was to carry out the first comprehensive analysis of adrenal steroid levels and steroidogenic enzyme expression in normal second trimester human fetuses...
February 12, 2018: BMC Medicine
https://www.readbyqxmd.com/read/29425150/aethiopinolones-a-e-new-pregnenolone-type-steroids-from-the-east-african-basidiomycete-fomitiporia-aethiopica
#16
Clara Chepkirui, Winnie C Sum, Tian Cheng, Josphat C Matasyoh, Cony Decock, Marc Stadler
A mycelial culture of the Kenyan basidiomycete Fomitiporia aethiopica was fermented on rice and the cultures were extracted with methanol. Subsequent HPLC profiling and preparative chromatography of its crude extract led to the isolation of five previously undescribed pregnenolone type triterpenes 1-5, for which we propose the trivial name aethiopinolones A-E. The chemical structures of the aethiopinolones were determined by extensive 1D- and 2D-NMR, and HRMS data analysis. The compounds exhibited moderate cytotoxic effects against various human cancer cell lines, but they were found devoid of significant nematicidal and antimicrobial activities...
February 9, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29424600/comparison-of-the-hepatic-and-thyroid-gland-effects-of-sodium-phenobarbital-and-pregnenolone-16%C3%AE-carbonitrile-in-wild-type-and-constitutive-androstane-receptor-car-pregnane-x-receptor-pxr-knockout-rats
#17
Corinne Haines, Lynsey R Chatham, Audrey Vardy, Clifford R Elcombe, John R Foster, Brian G Lake
1. The hepatic and thyroid gland effects of the constitutive androstane receptor (CAR) activator sodium phenobarbital (NaPB) and the pregnane X receptor (PXR) activator pregnenolone-16α-carbonitrile (PCN) were examined in male Sprague-Dawley wild type (WT) and knockout (KO) rats lacking both hepatic CAR and PXR receptors (CAR KO/PXR KO rats). 2. The treatment of WT rats for 7 days with 500 ppm NaPB in the diet and 100 mg/kg/day PCN by gavage resulted in increased relative liver weight, hepatocyte hypertrophy, increased hepatocyte replicative DNA synthesis (RDS) and induction of cytochrome P450 CYP2B and CYP3A subfamily enzymes...
February 9, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29421409/prenatal-exposure-to-glycol-ethers-and-sex-steroid-hormones-at-birth
#18
Charline Warembourg, Anne-Claire Binter, Frank Giton, Jean Fiet, Laurence Labat, Christine Monfort, Cécile Chevrier, Luc Multigner, Sylvaine Cordier, Ronan Garlantézec
BACKGROUND: Glycol ethers (GEs) are oxygenated solvents widely found in occupational and consumer water-based products. Some of them are well-known reproductive and developmental toxicants. OBJECTIVES: To study the variations in circulating sex steroid hormones, measured in cord blood, according to biomarkers of prenatal GE exposure. METHODS: The study population comes from the PELAGIE mother-child cohort, which enrolled pregnant women from Brittany (France, 2002-2006)...
January 31, 2018: Environment International
https://www.readbyqxmd.com/read/29420188/human-3beta-hydroxysteroid-dehydrogenase-deficiency-associated-with-normal-spermatic-numeration-despite-a-severe-enzyme-deficit
#19
Bruno Donadille, Muriel Houang, Irene Netchine, Jean-Pierre Siffroi, Sophie Christin-Maitre
Human 3 beta-hydroxysteroid dehydrogenase deficiency (3b-HSD) is a very rare form of congenital adrenal hyperplasia resulting from HSD3B2 gene mutations. Its estimated prevalence is less than 1/1,000,000 male neonates. It leads to steroidogenesis impairment in both adrenals and gonads. Few data are available on adult testicular function in such patients. Therefore, we evaluated gonadal axis and testicular function in a 46,XY adult patient, carrying a HSD3B2 mutation. The patient presented at birth with neonatal salt wasting syndrome, a micropenis, perineal hypospadias and intrascrotal testes...
February 2, 2018: Endocrine Connections
https://www.readbyqxmd.com/read/29402482/taxifolin-suppresses-rat-and-human-testicular-androgen-biosynthetic-enzymes
#20
Fei Ge, Erpo Tian, Li Wang, Xiaoheng Li, Qiqi Zhu, Yiyan Wang, Ying Zhong, Ren-Shan Ge
Taxifolin is a flavonoid. It has been used as a chemopreventive agent and supplement. It may have some beneficial effects to treat prostate cancer by suppressing androgen production in Leydig cells. The objective of the present study was to study the effects of taxifolin on androgen production of rat Leydig cells isolated from immature testis and some rat and human testosterone biosynthetic enzyme activities. Rat Leydig cells were incubated with 100μM taxifolin without (basal) or with 10ng/ml luteinizing hormone (LH), 10mM 8-bromoadenosine 3',5'-cyclic monophosphate (8BR), and steroid enzyme substrates (20μM): 22R-hydroxychloesterol, pregnenolone, progesterone, and androstenedione...
February 2, 2018: Fitoterapia
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