Memory-Enhancing Effects in Male Mice of Pregnenolone and Steroids
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Estrone Sulfate
Available online at www.sciencedirect.com Journal of Steroid Biochemistry & Molecular Biology 109 (2008) 158–167 Estrone sulfate (E1S), a prognosis marker for tumor aggressiveness in prostate cancer (PCa)ଝ Frank Giton a,∗, Alexandre de la Taille b, Yves Allory b, Herve´ Galons c, Francis Vacherot b, Pascale Soyeux b, Claude Clement´ Abbou b, Sylvain Loric b, Olivier Cussenot b, Jean-Pierre Raynaud d, Jean Fiet b a AP-HP CIB INSERM IMRB U841eq07, Henri Mondor, Facult´edeM´edecine, 94010 Cr´eteil, France b INSERM IMRB U841 eq07, CHU Henri Mondor, Facult´edeM´edecine, 94010 Cr´eteil, France c Service de Chimie organique, Facult´e de Pharmacie Paris V, 75006 Paris, France d Universit´e Pierre et Marie Curie, 75252 Paris, France Received 26 December 2006; accepted 26 October 2007 Abstract Seeking insight into the possible role of estrogens in prostate cancer (PCa) evolution, we assayed serum E2, estrone (E1), and estrone sulfate (E1S) in 349 PCa and 100 benign prostatic hyperplasia (BPH) patients, and in 208 control subjects in the same age range (50–74 years). E1 (pmol/L ± S.D.) and E1S (nmol/L ± S.D.) in the PCa and BPH patients (respectively 126.1 ± 66.1 and 2.82 ± 1.78, and 127.8 ± 56.4 and 2.78 ± 2.12) were significantly higher than in the controls (113.8 ± 47.6 and 2.11 ± 0.96). E2 was not significantly different among the PCa, BPH, and control groups. These assays were also carried out in PCa patients after partition by prognosis (PSA, Gleason score (GS), histological stage, and surgical margins (SM)). -
Pregnenolone Introduced 1997
Product Information Sheet – September 2016 Pregnenolone Introduced 1997 What Is It? • This product should not be taken by individuals with healthy levels of pregnenolone. Pregnenolone, 3-alpha-hydroxy-5-beta-pregnen-20-one, is a precursor to over 150 steroid hormones and is produced naturally in • Pregnenolone is best utilized by individuals over 40, and should the body from cholesterol. not be used to enhance athletic ability or endurance. Uses For Pregnenolone Are There Any Precautions Or Potential Side Memory Support: Animal studies have reported that pregnenolone Effects? may help to enhance memory by modulating N-methyl-D-aspartate Precautions: (NMDA) and gamma aminobutyrate (GABA) receptor activity in the brain. One study suggested that pregnenolone helped promote • NOT FOR USE BY INDIVIDUALS UNDER THE AGE OF 18. post-training task learning and memory.* • DO NOT USE IF PREGNANT OR NURSING. Immune Health: One study indicated that the 7-hydroxy metabolites • KEEP OUT OF REACH OF CHILDREN. from pregnenolone may help promote healthy immune system • Consult a physician or licensed qualified health professional before response.* using this product if you have, or have a family history of breast Mood Support: Pregnenolone has been reported to help promote cancer, prostate cancer, prostate enlargement, heart disease, low feelings of emotional well-being. One study suggested that “good” cholesterol (HDL), or if you are using any other dietary pregnenolone supported positive mood and feelings of motivation supplement, prescription drug, or over-the-counter drug. by mediating dopamine release.* • Do not exceed the recommended serving. Exceeding the What Is The Source? recommended serving may cause serious adverse health effects. -
Alteration of the Steroidogenesis in Boys with Autism Spectrum Disorders
Janšáková et al. Translational Psychiatry (2020) 10:340 https://doi.org/10.1038/s41398-020-01017-8 Translational Psychiatry ARTICLE Open Access Alteration of the steroidogenesis in boys with autism spectrum disorders Katarína Janšáková 1, Martin Hill 2,DianaČelárová1,HanaCelušáková1,GabrielaRepiská1,MarieBičíková2, Ludmila Máčová2 and Daniela Ostatníková1 Abstract The etiology of autism spectrum disorders (ASD) remains unknown, but associations between prenatal hormonal changes and ASD risk were found. The consequences of these changes on the steroidogenesis during a postnatal development are not yet well known. The aim of this study was to analyze the steroid metabolic pathway in prepubertal ASD and neurotypical boys. Plasma samples were collected from 62 prepubertal ASD boys and 24 age and sex-matched controls (CTRL). Eighty-two biomarkers of steroidogenesis were detected using gas-chromatography tandem-mass spectrometry. We observed changes across the whole alternative backdoor pathway of androgens synthesis toward lower level in ASD group. Our data indicate suppressed production of pregnenolone sulfate at augmented activities of CYP17A1 and SULT2A1 and reduced HSD3B2 activity in ASD group which is partly consistent with the results reported in older children, in whom the adrenal zona reticularis significantly influences the steroid levels. Furthermore, we detected the suppressed activity of CYP7B1 enzyme readily metabolizing the precursors of sex hormones on one hand but increased anti-glucocorticoid effect of 7α-hydroxy-DHEA via competition with cortisone for HSD11B1 on the other. The multivariate model found significant correlations between behavioral indices and circulating steroids. From dependent variables, the best correlation was found for the social interaction (28.5%). Observed changes give a space for their utilization as biomarkers while reveal the etiopathogenesis of ASD. -
The Relationship Between Serum Sex Steroid Levels and Heart Rate Variability Parameters in Males and the Effect Of
Türk Kardiyol Dern Arş - Arch Turk Soc Cardiol 2010;38(7):459-465 459 The relationship between serum sex steroid levels and heart rate variability parameters in males and the effect of age Erkeklerde serum cinsiyet steroidleri ile kalp hızı değişkenliği verileri arasındaki ilişki ve yaşın etkileri M. Tolga Doğru, M.D., M. Murad Başar, M.D.,# Ercan Yuvanç, M.D.,# Vedat Şimşek, M.D., Ömer Şahin, M.D. Departments of Cardiology and #Urology, Medicine Faculty of Kırıkkale University, Kırıkkale Objectives: We evaluated the relationships between sex Amaç: Bu çalışmada cinsiyet steroidleri ile kalp hızı de- steroid levels and heart rate variability (HRV) parameters. ğişkenliği (KHD) verileri arasındaki ilişkiler araştırıldı. Study design: The study included 114 male subjects (mean Çalışma planı: Çalışmaya, kardiyolojik açıdan değerlen- age 46.6±11.3 years) presenting to our department for cardi- dirme için başvuran 114 erkek hasta (ort. yaş 46.6±11.3) ologic evaluation. Hormonal analysis included serum levels alındı. Hormon analizlerinde serumda luteinize edici hor- of luteinizing hormone, prolactin, total testosterone (TT), free mon, prolaktin, total testosteron (TT), serbest testosteron, testosterone, estradiol (E2), and dehydroepiandrosterone östradiol (E2) ve dehidroepiandrosteron sülfat (DHEA-S) sulfate (DHEA-S). Parameters of HRV were derived from düzeyleri ölçüldü. Yirmi dört saatlik Holter kayıtlarından 24-hour Holter monitoring. The associations between serum KHD parametreleri hesaplandı. Serum cinsiyet steroidleri sex steroid levels and HRV parameters were investigated in ile KHD değerleri arasındaki ilişkiler hastalar üç yaş gru- three age groups (20-39 years; 40-59 years; >60 years). buna (20-39 yaş; 40-59 yaş; >60 yaş) ayrılarak incelendi. -
Conjugated and Unconjugated Plasma Androgens in Normal Children
Pediat. Res. 6: 111-118 (1972) Androstcncdionc sexual development dehydroepiandrosterone testosterone Conjugated and Unconjugated Plasma Androgens in Normal Children DONALD A. BOON,'291 RAYMOND E. KEENAN, W. ROY SLAUNWHITE, JR., AND THOMAS ACETO, JR. Children's Hospital, Medical Foundation of Buffalo, Roswell Park Memorial Institute, and Departments of Biochemistry and Pediatrics, School of Medicine, State University of New York at Buffalo, Buffalo, New York, USA Extract Methods developed in this laboratory permit measurement of the androgens, testos- terone (T), dehydroepiandrosterone (D), and androstenedione (A) on a 10-ml sample of plasma. We have determined concentrations of the unconjugated androgens (T, A, D) as well as of the sulfates of dehydroepiandrosterone (DS) and androsterone (AS) in the plasma of 85 healthy children of both sexes from birth through the age of 20 years. Our results are shown and summarized, along with those of other investigators. Mean plasma concentrations Sex and age ng/100 ml Mg/100 ml T A D AS DS Male Neonates 39 24 30 None detectable None detectable 1-8 years 25 58 64 2 11 9-20 years 231 138 237 28 74 Female Neonates 36 30 83 None detectable None detectable 1-8 years 11 69 54 5 20 9-20 years 28 84 164 22 44 Testosterone was elevated in both sexes in the newborn as compared with the 1-8- year-old group. In contrast, sulfated androgens, with one exception, were undetectable early in life. In males, there was a marked rise in all androgens, especially T, in the 9-18-year-old group. -
Comparison of Pregnenolone Sulfate, Pregnanolone and Estradiol Levels
Rustichelli et al. The Journal of Headache and Pain (2021) 22:13 The Journal of Headache https://doi.org/10.1186/s10194-021-01231-9 and Pain SHORT REPORT Open Access Comparison of pregnenolone sulfate, pregnanolone and estradiol levels between patients with menstrually-related migraine and controls: an exploratory study Cecilia Rustichelli1, Elisa Bellei2, Stefania Bergamini2, Emanuela Monari2, Flavia Lo Castro3, Carlo Baraldi4, Aldo Tomasi2 and Anna Ferrari4* Abstract Background: 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. Methods: 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-tandem mass spectrometry, while estradiol levels by enzyme-linked immunosorbent assay. Results: Serum levels of pregnenolone sulfate and pregnanolone were significantly lower in the MM group than in controls (pregnenolone sulfate: P = 0.0328; pregnanolone: P = 0.0271, Student’s t-test), while estradiol levels were similar. In MM group, pregnenolone sulfate serum levels were negatively correlated with history of migraine (R2 = 0.1369; P = 0.0482) and age (R2 = 0.2826, P = 0.0025) while pregnenolone sulfate levels were not age-related in the control group (R2 = 0.04436, P = 0.4337, linear regression analysis). -
Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act
Updated June 07, 2021 Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act Three categories of bulk drug substances: • Category 1: Bulk Drug Substances Under Evaluation • Category 2: Bulk Drug Substances that Raise Significant Safety Risks • Category 3: Bulk Drug Substances Nominated Without Adequate Support Updates to Categories of Substances Nominated for the 503B Bulk Drug Substances List1 • Add the following entry to category 2 due to serious safety concerns of mutagenicity, cytotoxicity, and possible carcinogenicity when quinacrine hydrochloride is used for intrauterine administration for non- surgical female sterilization: 2,3 o Quinacrine Hydrochloride for intrauterine administration • Revision to category 1 for clarity: o Modify the entry for “Quinacrine Hydrochloride” to “Quinacrine Hydrochloride (except for intrauterine administration).” • Revision to category 1 to correct a substance name error: o Correct the error in the substance name “DHEA (dehydroepiandosterone)” to “DHEA (dehydroepiandrosterone).” 1 For the purposes of the substance names in the categories, hydrated forms of the substance are included in the scope of the substance name. 2 Quinacrine HCl was previously reviewed in 2016 as part of FDA’s consideration of this bulk drug substance for inclusion on the 503A Bulks List. As part of this review, the Division of Bone, Reproductive and Urologic Products (DBRUP), now the Division of Urology, Obstetrics and Gynecology (DUOG), evaluated the nomination of quinacrine for intrauterine administration for non-surgical female sterilization and recommended that quinacrine should not be included on the 503A Bulks List for this use. This recommendation was based on the lack of information on efficacy comparable to other available methods of female sterilization and serious safety concerns of mutagenicity, cytotoxicity and possible carcinogenicity in use of quinacrine for this indication and route of administration. -
Pregnenolone, a Fruit of Cholesterol
PREGNENOLONE, A FRUIT OF CHOLESTEROL Mother of Progesterone & D.H.E.A. The following information comes from Dr. Ray Peat, who has done pioneering research on the anti-aging steroids, pregnenolone, progesterone and DHEA (Dehydroepiandrosterone). I have included excerpts from his writings plus the results of interviews. Research references are provided when available, but in many cases, I could only describe the group of researchers who did the experiment. My purpose for this article is not to start a riot but to illustrate why I think it’s dangerous to artificially inhibit cholesterol formation in your body with drugs and synthetic foods. Dr. Peat accidentally discovered the effects of pregnenolone when he took some vitamin E containing a residue of pregnenolone that was left over from an experiment in solubility. Peat had been suffering from a variety of complaints, including " inflammation of the arteries, dental abscesses, asthma, migraines, and colitis ." When he took the vitamin E containing some pregnenolone in the vitamin E, he crawled out of his sick bed, took a pinch of pure pregnenolone and felt immediately better. All of his symptoms gradually disappeared and in ten weeks, his appearance changed. Many aging characteristics, such as sagging skin, "chicken neck," bags under the eyes, etc. receded. These changes were dramatically reported in a passport photo, taken one year before pregnenolone and another one taken 10 weeks after pregnenolone therapy was initiated. I regret that the original photos are not available for inclusion here. When I saw this photo, presented in one of his newsletters, I fell off my chair, dashed to the phone and called Dr. -
Neurosteroids: Pregnenolone in Human Sciatic Nerves
Proc. Natl. Acad. Sci. USA Vol. 89, pp. 6790-6793, August 1992 Neurobiology Neurosteroids: Pregnenolone in human sciatic nerves (dehydroepiandrosterone/mass spectrometry/steroid sulfates/steroid fatty acid esters) ROBERT MORFIN*t, JACQUES YOUNG*, COLETTE CORPtCHOT*, BORJE EGESTADt, JAN SJOVALLt, AND ETIENNE-EMILE BAULIEU*§ *Institut National de la Santd et de la Recherche MWdicale U33, Laboratoire Hormones, 94276 Bicetre Cedex, France; and tDepartment of Physiological Chemistry, Karolinska Institutet, Stockholm, Sweden Contributed by Etienne-Emile Baulieu, March 30, 1992 ABSTRACT The characterization and quantification of Tissues. Tissues were obtained <48 hr after death from pregnenolone in human sciatic nerves were undertaken, fol- cadavers of both sexes bequeathed to medical research. lowing previous demonstration of the synthesis of this steroid Corpses were kept refrigerated at 40C. Ages ranged from 44 in rat brain oligodendrocytes, to explore the hypothesis that to 90 years. Causes of death were not recorded. Portions of Schwann cells may demonstrate the same biosynthetic activity. sciatic nerves, tendons, and muscle were taken close to the Pregnenolone was definitively identified by mass spectrometry knee. Samples of spleen were obtained in one case. The and quantified by specific radioinmunoassay. Its concentra- collected samples (0.675-4.870 g) were first weighed and then tion (mean ± SD, 63.9 ± 45.9 ng/g of wet tissue, n = 12) was frozen in liquid nitrogen until processed further. 2100 times the plasma level and concentration found in Extraction and Purification Procedures. Frozen samples in tendons and muscle. No correlation was found with sex or age. liquid nitrogen were first pulverized in a mortar and then Free dehydroepiandrosterone as well as sulfate and fatty acid homogenized in phosphate-buffered saline at 40C. -
Memory-Enhancing Effects in Male Mice of Pregnenolone and Steroids Metabolically Derived from It
Proc. Nati. Acad. Sci. USA Vol. 89, pp. 1567-1571, March 1992 Neurobiology Memory-enhancing effects in male mice of pregnenolone and steroids metabolically derived from it (memory enhancement/pregnenolone sulfate/receptors/immediate-early genes/aging) JAMES F. FLOOD*t, JOHN E. MORLEY*, AND EUGENE ROBERTSt§ *Genatnc Research Education and Clinical Center, Veterans Administration Medical Center, St. Louis, MO 63106, and St. Louis University School of Medicine, Division of Geriatric Medicine, St. Louis, MO 63104; and tDepartment of Neurobiochemistry, Beckman Research Institute of the City of Hope, Duarte, CA 91010 Contributed by Eugene Roberts, November 8, 1991 ABSTRACT Immediate post-training intracerebroven- postmitotic differentiated states was favored in both neurons tricular administration to male mice of pregnenolone (P), and glia (7, 8). pregnenolone sulfate (PS), dehydroepiandrosterone (DHEA), The water-soluble DHEAS, administered intracerebro- dehydroepiandrosterone sulfate (DHEAS), androstenedione, ventricularly (i.c.v.) or subcutaneously (s.c.) after training, testosterone, dihydrotestosterone, or aldosterone caused im- showed convincing memory-enhancing (ME) effects in foot- provement ofretention for footshock active avoidance training, shock active avoidance training (FAAT) in undertrained male while estrone, estradiol, progesterone, or 16.8-bromoepi- mice. DHEAS administered i.c.v. facilitated retention for androsterone did not. Dose-response curves were obtained for step-down passive avoidance training. Retention of FAAT P, PS, DHEA, and testosterone. P and PS were the most potent, was improved when DHEAS was given in taste-camouflaged PS showing significant effects at 3.5 fmol per mouse. The active drinking water for 1 week before and 1 week after training, steroids did not show discernible structural features or known while DHEAS in the drinking water for 2 weeks did not membrane or biochemical effects that correlated with their improve acquisition (9). -
Introduction Endocannabinoid System Cannabinoid Tetrad THC, CB1 And
Natural Defense Against THC Overdose Type-1 Cannabinoid Receptors and the Functional Effects of Pregnenolone Brigitte Rios Llamosa and Alexis Camacho Advisor: Mr. Justin Spaeth, Messmer High School, Milwaukee WI Mentor: Dr. Aaron Miller - Assistant Professor of Physiology at Concordia University Introduction THC, CB1 and Pregnenolone CB1 Receptor Model Cannabis, often referred to as marijuana, is a drug produced from the Cannabis plant. Tetrahydrocannabinol (THC), the active ingredient in marijuana, also activates the CB1 Recently, marijuana has become an often debated topic as people work to legalize its use receptor. THC and similar drugs have therapeutic potential in the treatment of pain, Our model highlights the amino acids E133 and R409, which for both recreational (as in Colorado) and medical purposes. Marijuana is able to help Alzheimer’s disease, anxiety, arthritis, and cancer. A downside to the medicinal use of form hydrogen bonds with pregnenolone and are required for relieve pain, but it can also lower performance in everyday tasks. THC is that it also induces psychotropic effects. its binding to the allosteric site of CB1. Negatives Positives Both of these amino acids are colored in cpk color and • Poor coordination of • Can help control connected with a strut to our pregnenolone molecule. Other movement epileptic seizures areas that are highlighted are color-coded as follows: • Afterwards, users feel • May decrease anxiety tired or depressed • Can slow progression Alpha helixes are red. • Increases heartbeat and of diseases such as risk of heart attack Alzheimer’s disease Struts are colored white. • Inability to understand • Has been used to treat Non-motif portions are colored cornflower blue. -
Steroid Secretion. Newly Discovered Functions in the Brain
Steroid secretion. Newly Discovered Functions in the Brain. Fundamental and Clinical considerations. Bernardo O. Dubrovsky McGill University Medical School Montreal, Quebec, Canada B.O. Dubrovsky, 3445 Drummond Street, #701, Montreal, Quebec, H3G 1X9,Canada. Tel: (514) 844-5702 Fax: (514) 398-4370 E-mail: [email protected] Abstract While the relationships between endocrines and psychiatry have long been established, the implications of neurosteroid (NS) hormones, identified in the early 1980s for psychopathology, started to be recognized in the nineties. Tetrahydro metabolites of progesterone (ATHP) and deoxycorticosterone (ATHDOC) act as positive allosteric modulators of neurotransmitter receptors such as GABAA. Other NSs, i.e., androsterone, pregnenolone, dehydroepiandrosterone (DHEA), their sulfates and lipid derivatives modulate glycine-activated chloride channels, neural nicotinic acetylcholine receptors constituted in Xenopus laevis oocytes, and voltage-activated calcium channels. Sigma receptors, as pharmacologically defined by their effect on N-methyl-D- aspartate (NMDA) activity, have been studied in rat hippocampal preparations: here DHEAS acts as a sigma receptor agonist, differently from pregnenolone which appears as a sigma inverse agonist and progesterone which behaves as an antagonist. All of them were identified as NSs. Neuroactive steroids rapidly change CNS excitability and produce behavioral effects within seconds to minutes following administration to both laboratory animals and man. These fast actions probably indicate membrane mediated effects. This notwithstanding, Rupprecht et al. showed that after oxidation, ring A reduced pregnanes can regulate gene expression via the progesterone intracellular receptor. The necessary enzymes for the metabolism of primary adrenal and gonadal steroids, a peripheral source for NSs, exist in the brain in a compartmentalized way.