Convergence of Multiple Mechanisms of Steroid Hormone Action

Total Page:16

File Type:pdf, Size:1020Kb

Convergence of Multiple Mechanisms of Steroid Hormone Action Review 569 Convergence of Multiple Mechanisms of Steroid Hormone Action Authors S. K. Mani 1 * , P. G. Mermelstein 2 * , M. J. Tetel 3 * , G. Anesetti 4 * Affi liations 1 Department of Molecular & Cellular Biology and Neuroscience, Baylor College of Medicine, Houston, TX, USA 2 Department of Neuroscience, University of Minnesota, Minneapolis, MN, USA 3 Neuroscience Program, Wellesley College, Wellesley, MA, USA 4 Departamento de Hostologia y Embriologia, Facultad de Medicine, Universidad de la Republica, Montevideo, Uruguay Key words Abstract receptors can also be activated in a “ligand-inde- ● ▶ estrogen ▼ pendent” manner by other factors including neu- ● ▶ progesterone Steroid hormones modulate a wide array of rotransmitters. Recent studies indicate that rapid, ▶ ● signaling physiological processes including development, nonclassical steroid eff ects involve extranuclear ● ▶ cross-talk metabolism, and reproduction in various species. steroid receptors located at the membrane, which ● ▶ ovary ● ▶ brain It is generally believed that these biological eff ects interact with cytoplasmic kinase signaling mol- are predominantly mediated by their binding to ecules and G-proteins. The current review deals specifi c intracellular receptors resulting in con- with various mechanisms that function together formational change, dimerization, and recruit- in an integrated manner to promote hormone- ment of coregulators for transcription-dependent dependent actions on the central and sympathetic genomic actions (classical mechanism). In addi- nervous systems. tion, to their cognate ligands, intracellular steroid Abbreviations gene expression and function. Interestingly, not ▼ all the “classical” receptors are intranuclear and CBP CREB binding protein can be associated at the membrane. As described CRE CREB response element in this review, extranuclear ERs and PRs at the DAR Dopamine receptor (DAR) membrane or in the cytoplasm can interact with ER Estrogen receptor G proteins and signaling kinases, and other G received 13 . 12 . 2011 ERE Estrogen response element protein coupled receptors, to mediate rapid accepted 24 . 02 . 2012 mGluR Metabotropic glutamate receptor eff ects of the hormones. The rapid actions involv- PGMRC1 Progesterone membrane receptor ing cytoplasmic kinase signaling and/or extra- Bibliography nuclear steroid receptors can result in both DOI http://dx.doi.org/ component 1 10.1055/s-0032-1306343 PR Progestin receptor transcription-independent and transcription- Published online: PRE Progestin response element dependent actions. In addition, to their cognate March 27, 2012 SRCs Steroid receptor coactivators ligands, intranuclear steroid receptors (PRs) can Horm Metab Res 2012; also be activated in a “ligand-independent” man- 44: 569–576 ner by neurotransmitters (dopamine; DA). In this © Georg Thieme Verlag KG Introduction review, the distinct classical and nonclassical cel- Stuttgart · New York lular and molecular mechanisms of steroid hor- ISSN 0018-5043 ▼ Steroid hormones, estradiol (E2 ) and progester- mone action will be discussed with specifi c Correspondence one (P), regulate important physiological proc- reference to E2 and P eff ects in central and sym- S. K. Mani esses including development, diff erentiation, pathetic nervous systems ( ● ▶ Fig. 1 ) . Department of Molecular & metabolism, reproduction, learning, and mem- Cellular Biology ory in various species. The biological eff ects of E2 Baylor College of Medicine and P are primarily mediated by binding to their Mechanisms of Progesterone Action in One Baylor Plaza classical intranuclear receptors, estrogen (ERs) Brain Houston Texas 77030 and progestin receptors (PRs) that act as ligand- ▼ USA inducible transcription factors and interact with Ovarian steroid hormones, E2 and P regulate cel- Tel.: +1/713/798 6647 steroid receptor coregulators to modulate target lular functions in the central nervous system Fax: +1/713/790 1275 resulting in alterations in physiology and repro- [email protected] * All the authors contributed equally to this work. Mani SK et al. Mechanisms of Steroid Hormone Action … Horm Metab Res 2012; 44: 569–576 570 Review Fig. 1 Convergence of progesterone- and estradiol-mediated signaling in the nervous system. Through membrane, cytosolic, and intra- cellular receptors, these hormones aff ect surface membrane signaling, second messenger systems, and gene expression. Transcriptional co-factors are also intimately involved in the regulation of classical, steroid hormone-mediated as well as activity-dependent gene expression. ductive behavior. As in other steroid-sensitive tissues, the regu- female sexual receptive behavior has been demonstrated latory action of E2 on behavior is believed to involve the [ 18 , 19 ] . In addition, DA-initiated second messenger signaling activation of ERs, altering the expression of a number of genes, cascade was demonstrated to involve the activation of protein including PR gene. Progestins, including P, exert their physiolog- kinase A (PKA) and neuronal phosphoprotein, dopamine and ical eff ects primarily by binding to E2 -induced, intracellular PRs, cAMP regulated phosphoprotein-32 (DARPP-32) [ 20 ] . This sign- which function as transcriptional factors, regulating the expres- aling mechanism could potentially lead to the alterations in the sion of genes and genomic neural networks to initiate and/or phosphorylation dynamics and activation of PRs and/or its sustain physiological response [ 1 , 2 ] . PRs undergo signifi cant coregulators as discussed below. conformational change upon binding by P, leading to their While genomic eff ects characterized by a delayed onset have nuclear translocation, dimerization and DNA binding [ 3 ] . When traditionally been assumed to be the primary pathway for P bound to DNA, PRs interact with basal transcriptional machin- action in the brain, recent studies suggest the involvement of ery, assisted by coactivator molecules to initiate chromatin “nonclassical” mechanisms of progesterone action. These non- remodeling [ 4 – 6 ] . Phosphorylation of the coactivators also plays classical short-latency eff ects of progesterone widely aff ect cell a crucial role in the activation of steroid receptors [ 7 , 8 ] . The role functioning, through modulation of putative cell surface recep- of coactivators is discussed below. tors, ion channels and mechanisms coupled to cytoplasmic Spatial, temporal, and functional correlations indicate that E2 - second messenger signaling cascades, independent of gene tran- induced PRs function as transcriptional mediators and regulate scription [ 21 – 23 ] . In addition to P, several of its ring-A reduced transcription of target genes to aff ect reproductive behavior [ 2 ] . metabolites have been shown to facilitate lordosis response in The time course of activation and termination of reproductive ovariectomized, E2 -primed female rats via activation of MAPK behavior has also been shown to parallel E2 -induced increase pathway [ 17 ] . A number of laboratories have reported the and decline in PRs in the hypothalamus and the preoptic areas of involvement of at least 4 extranuclear kinase systems, PKA, PKC, the brain. A wide body of literature has identifi ed diff erent neu- CaMKII, and PKG in the rapid P eff ects in the VMH and POA of the roanatomical sites in the regulation of female sexual behavior by female rat [ 16 , 17 , 21 , 24 – 27 ] . Since the initiation of these non- steroid hormones [ 9 ] . Studies using PR antagonists, protein and classical eff ects occurs rapidly (in seconds or minutes) and is RNA synthesis inhibitors, antisense to oligonucleotides to PRm- triggered at the membrane surface, the classical model of RNA and PR mutant mice indicate a requirement for classical nuclear PR-mediation is inadequate to account for these eff ects. genomic mode of activation involving intracellular PRs in Recent evidence suggests the involvement of 2 types of novel P-mediated facilitation of reproductive behavior [ 10 – 15 ] . membrane proteins unrelated to classical PRs, progesterone Studies have also demonstrated that PRs can be activated by fac- membrane receptor component 1 (PGMRC1) and progesterone tors other than their cognate ligand, P (ligand-independent membrane receptors (mPRs), in P signaling in several reproduc- activation). Second messenger molecules, including 3′,5′-cyclic tive tissues and in the brain [ 28 , 29 ] . Inhibition of MAPK signaling adenosine monophosphate (cAMP), 3′,5′-cyclic guanosine mono- pathway results in reduction of P, dibutyryl-cAMP (db-cAMP)-, phosphate (cGMP), nitric oxide (NO), and neurotransmitter prostaglandin E 2 (PGE2 )-, or GnRH-facilitated female reproductive (dopamine, DA) can substitute for P in the facilitation of repro- behavior in rats [ 17 ] . These studies suggest that E2 and P actions ductive behavior [ 16 , 17 ] . Using PR antagonists, antisense oligo- in the brain could involve rapid activation of multiple signal nucleotides and null mutants for PRs, the critical requirement of transduction pathways that converge with classical genomic classical PRs as transcriptional mediators in the cross talk pathways. between P and DA-initiated pathways in the facilitation of Mani SK et al. Mechanisms of Steroid Hormone Action … Horm Metab Res 2012; 44: 569–576 Review 571 Nuclear Receptor Coactivators: The p160 Steroid expressed at high levels in the hypothalamus, cortex and hip- Receptor Coactivator Family pocampus of rodents [ 34 – 43 ] and birds [ 44 – 47 ] . Interestingly, in ▼ contrast with the other members of the SRC family,
Recommended publications
  • Neurosteroid Metabolism in the Human Brain
    European Journal of Endocrinology (2001) 145 669±679 ISSN 0804-4643 REVIEW Neurosteroid metabolism in the human brain Birgit Stoffel-Wagner Department of Clinical Biochemistry, University of Bonn, 53127 Bonn, Germany (Correspondence should be addressed to Birgit Stoffel-Wagner, Institut fuÈr Klinische Biochemie, Universitaet Bonn, Sigmund-Freud-Strasse 25, D-53127 Bonn, Germany; Email: [email protected]) Abstract This review summarizes the current knowledge of the biosynthesis of neurosteroids in the human brain, the enzymes mediating these reactions, their localization and the putative effects of neurosteroids. Molecular biological and biochemical studies have now ®rmly established the presence of the steroidogenic enzymes cytochrome P450 cholesterol side-chain cleavage (P450SCC), aromatase, 5a-reductase, 3a-hydroxysteroid dehydrogenase and 17b-hydroxysteroid dehydrogenase in human brain. The functions attributed to speci®c neurosteroids include modulation of g-aminobutyric acid A (GABAA), N-methyl-d-aspartate (NMDA), nicotinic, muscarinic, serotonin (5-HT3), kainate, glycine and sigma receptors, neuroprotection and induction of neurite outgrowth, dendritic spines and synaptogenesis. The ®rst clinical investigations in humans produced evidence for an involvement of neuroactive steroids in conditions such as fatigue during pregnancy, premenstrual syndrome, post partum depression, catamenial epilepsy, depressive disorders and dementia disorders. Better knowledge of the biochemical pathways of neurosteroidogenesis and
    [Show full text]
  • Steroid Hormones
    Chemical Signaling Hormonal Signal Transduction Pathways Types of Chemical Signaling Chemical signaling between cells is one of the most important ways that activities of tissues and organs are coordinated. The nervous system is the other major coordinating system in animals, but even here chemical signaling is used between adjacent neurons. Three major types: Sites of Hormone Release More commonly, especially in the vertebrates, the sources of hormones are specialized glands called endocrine glands. Even here the source of the hormone is often modified nerve cells or neurosecretory cells. Some organs that have other functions also release hormones - for example, many hormones are released by different organs of the digestive system. Types of Responses Controlled by Hormones Hormones are not only used for long-distance signaling around the body, but they also provide for more prolonged regulatory responses. Prolonged responses can persist for minutes, hours, or even many days. Examples include maintenance of blood osmolarity, blood glucose, metabolic rate of specific tissues, control of reproductive cycles. The nervous system is used for more rapid responses of shorter duration. Example of Regulation of Blood Glucose Types of Hormones 1) Amines: Catecholamines, epinephrine and norepinephrine, derived from amino acids 2) Prostaglandins: Cyclic unsaturated fatty acids Types of Hormones 3) Steroid hormones: Include testosterone and estrogen, cyclic hydrocarbons derived from cholesterol. 4) Peptides and proteins: Include insulin Three Steps in Cell Signaling Target organ specificity is the result of specific receptor molecules for the hormone, either on the plasma membrane surface, or in some cases in the cytoplasm, of cells in the target organ.
    [Show full text]
  • Dehydroepiandrosterone an Inexpensive Steroid Hormone That Decreases the Mortality Due to Sepsis Following Trauma-Induced Hemorrhage
    PAPER Dehydroepiandrosterone An Inexpensive Steroid Hormone That Decreases the Mortality Due to Sepsis Following Trauma-Induced Hemorrhage Martin K. Angele, MD; Robert A. Catania, MD; Alfred Ayala, PhD; William G. Cioffi, MD; Kirby I. Bland, MD; Irshad H. Chaudry, PhD Background: Recent studies suggest that male sex ste- hemorrhage and resuscitation, the animals were killed roids play a role in producing immunodepression follow- and blood, spleens, and peritoneal macrophages were har- ing trauma-hemorrhage. This notion is supported by stud- vested. Splenocyte proliferation and interleukin (IL) 2 ies showing that castration of male mice before trauma- release and splenic and peritoneal macrophage IL-1 and hemorrhage or the administration of the androgen receptor IL-6 release were determined. In a separate set of experi- blocker flutamide following trauma-hemorrhage in non- ments, sepsis was induced by cecal ligation and punc- castrated animals prevents immunodepression and im- ture at 48 hours after trauma-hemorrhage and resusci- proves the survival rate of animals subjected to subse- tation. For those studies, the animals received vehicle, a quent sepsis. However, it remains unknown whether the single 100-µg dose of DHEA, or 100 µg/d DHEA for 3 most abundant steroid hormone, dehydroepiandros- days following hemorrhage and resuscitation. Survival terone (DHEA), protects or depresses immune functions was monitored for 10 days after the induction of sepsis. following trauma-hemorrhage. In this regard, DHEA has been reported to have estrogenic and androgenic proper- Results: Administration of DHEA restored the de- ties, depending on the hormonal milieu. pressed splenocyte and macrophage functions at 24 hours after trauma-hemorrhage.
    [Show full text]
  • Low Testosterone (Hypogonadism)
    Low Testosterone (Hypogonadism) Testosterone is an anabolic-androgenic steroid hormone which is made in the testes in males (a minimal amount is also made in the adrenal glands). Testosterone has two major functions in the human body. Testosterone production is regulated by hormones released from the brain. The brain and testes work together to keep testosterone in the normal range (between 199 ng/dL and 1586 ng/dL) Testosterone is needed to form and maintain the male sex organs, regulate sex drive (libido) and promote secondary male sex characteristics such as voice deepening and development of facial and body hair. Testosterone facilitates muscle growth as well as bone development and maintenance. Low testosterone levels in the blood are seen in males with a medical condition known as Hypogonadism. This may be due to a signaling problem between the brain and testes that can cause production to slow or stop. Hypogonadism can also be caused by a problem with production in the testes themselves. Causes Primary: This type of hypogonadism — also known as primary testicular failure — originates from a problem in the testicles. Secondary: This type of hypogonadism indicates a problem in the hypothalamus or the pituitary gland — parts of the brain that signal the testicles to produce testosterone. The hypothalamus produces gonadotropin- releasing hormone, which signals the pituitary gland to make follicle-stimulating hormone (FSH) and luteinizing hormone. Luteinizing hormone then signals the testes to produce testosterone. Either type of hypogonadism may be caused by an inherited (congenital) trait or something that happens later in life (acquired), such as an injury or an infection.
    [Show full text]
  • The Orphan Receptor Rev-Erbaot Activates Transcription Via a Novel Response Element HEATHER P
    MOLECULAR AND CELLULAR BIOLOGY, May 1993, p. 3113-3121 Vol. 13, No. 5 0270-7306/93/053113-09$02.00/0 Copyright © 1993, American Society for Microbiology The Orphan Receptor Rev-ErbAot Activates Transcription via a Novel Response Element HEATHER P. HARDING AND MITCHELL A. LAZAR* Endocrinology Division, Department ofMedicine, and Department of Genetics, University ofPennsylvania School ofMedicine, Philadelphia, Pennsylvania 19104 Received 18 December 1992/Returned for modification 1 February 1993/Accepted 11 February 1993 Rev-ErbAca (Rev-Erb) is a nuclear hormone receptor-related protein encoded on the opposite strand of the at-thyroid hormone receptor (TR) gene. This unusual genomic arrangement may have a regulatory role, but the conservation of human and rodent Rev-Erb amino acid sequences suggests that the protein itself has an important function, potentially as a sequence-specific transcriptional regulator. However, despite its relation- ship to the TR, Rev-Erb bound poorly to TR binding sites. To determine its DNA-binding specificity in an unbiased manner, Rev-Erb was synthesized in Escherichia coli, purified, and used to select specific binding sites from libraries of random double-stranded DNA sequences. We found that Rev-Erb binds to a unique site consisting of a specific 5-bp A/T-rich sequence adjacent to a TR half-site. Rev-Erb contacts this entire asymmetric 11-bp sequence, which is the longest nonrepetitive element specifically recognized by a member of the thyroid/steroid hormone receptor superfamily, and mutations in either the A/T-rich or TR half-site regions abolished specific binding. The binding specificity of wild-type Rev-Erb was nearly identical to that of C- and N-terminally truncated forms.
    [Show full text]
  • Analysis of Anabolic Steroid Glucuronide and Sulfate Conjugates
    Applicability of an innovative steroid-profiling method to determine synthetic growth promoter abuse in cattle Blokland, M.H.; Tricht, E.F. van; Ginkel L.A. van; Sterk, S.S. This is a "Post-Print" accepted manuscript, which has been published in “Catena” This version is distributed under a non-commencial no derivatives Creative Commons (CC-BY-NC-ND) user license, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited and not used for commercial purposes. Further, the restriction applies that if you remix, transform, or build upon the material, you may not distribute the modified material. Please cite this publication as follows: Blokland, M.H.; Tricht, E.F. van; Ginkel L.A. van; Sterk, S.S. (2017) Applicability of an innovative steroid-profiling method to determine synthetic growth promoter abuse in cattle. The Journal of Steroid Biochemistry and Molecular Biology 174, p. 265-275 You can download the published version at: https://doi.org/10.1016/j.jsbmb.2017.10.007 Applicability of an innovative steroid-profiling method to determine synthetic growth promoter abuse in cattle 5 M.H. Blokland*, E.F. van Tricht, L.A van Ginkel, S.S. Sterk RIKILT Wageningen University & Research, P.O. Box 230, Wageningen, The Netherlands 10 *Corresponding author: M.H. Blokland, Tel.: +31 317 480417, E-mail: [email protected] 15 Keywords: synthetic steroids, growth promoters, cattle, UHPLC-MS/MS, steroid profiling, steroidogenesis Abstract 20 A robust LC-MS/MS method was developed to quantify a large number of phase I and phase II steroids in urine.
    [Show full text]
  • Chapter 9 Cell Signaling Events
    Chapter 9 Cell Signaling Events © 2020 Elsevier Inc. All rights reserved. Figure 9–1. Fibroblast growth factor (FGF) signal transduction pathways. Activated FGF receptors (FGFRs; red rectangles) stimulate the phospholipase Cγ (PLCγ) pathway (blue highlight), the phosphatidylinositol 3-kinase (PI3K)-AKT/protein kinase B (PKB) pathway (yellow highlight), and the FRS2-RAS-mitogen-activated protein kinase (MAPK) pathway (green highlight). The activated MAPKs (extracellular signal-regulated kinases (ERKs), p38, or c-Jun N-terminal kinases (JNKs)) are translocated to the nucleus where they phosphorylate (P) transcription factors, thereby regulating target genes. (Modified from Dailey L, et al. Cytokine Growth Factor Rev 2005;16:233, by permission.) © 2020 Elsevier Inc. All rights reserved. 2 Figure 9–2. Activation and feedback regulation of the MAPK pathway. The classical MAPK pathway is activated in human tumors by upstream receptor tyrosine kinases (RTKs) or by mutations in RAS, BRAF, and MEK1. RTKs activate RAS by recruiting adaptor proteins (e.g., GRB-2) and exchange factors (e.g., Sos). RAS activation promotes the formation of RAF dimers, which activate MEK-ERK cascade through phosphorylation. ERK pathway activity is regulated by negative feedback at multiple levels, including the transcriptional activation of DUSP proteins that negatively regulate the pathway. ERK also phosphorylates and thus regulates CRAF and MEK activity directly. ERK, or its immediate substrate RSK, also phosphorylates Sos at several residues, inhibiting its activity and thus negatively regulating RAS activity. (From Liu, et al., Acta Pharm Sin B 2018;8(4):552–562.) © 2020 Elsevier Inc. All rights reserved. 3 Figure 9–3. PI3 kinase-AKT pathway mutations in cancer.
    [Show full text]
  • Plasma Membrane Receptors for Steroid Hormones in Cell Signaling and Nuclear Function
    Chapter 5 / Plasma Membrane Receptors for Steroids 67 5 Plasma Membrane Receptors for Steroid Hormones in Cell Signaling and Nuclear Function Richard J. Pietras, PhD, MD and Clara M. Szego, PhD CONTENTS INTRODUCTION STEROID RECEPTOR SIGNALING MECHANISMS PLASMA MEMBRANE ORGANIZATION AND STEROID HORMONE RECEPTORS INTEGRATION OF MEMBRANE AND NUCLEAR SIGNALING IN STEROID HORMONE ACTION MEMBRANE-ASSOCIATED STEROID RECEPTORS IN HEALTH AND DISEASE CONCLUSION 1. INTRODUCTION Steroid hormones play an important role in coordi- genomic mechanism is generally slow, often requiring nating rapid, as well as sustained, responses of target hours or days before the consequences of hormone cells in complex organisms to changes in the internal exposure are evident. However, steroids also elicit and external environment. The broad physiologic rapid cell responses, often within seconds (see Fig. 1). effects of steroid hormones in the regulation of growth, The time course of these acute events parallels that development, and homeostasis have been known for evoked by peptide agonists, lending support to the con- decades. Often, these hormone actions culminate in clusion that they do not require precedent gene activa- altered gene expression, which is preceded many hours tion. Rather, many rapid effects of steroids, which have earlier by enhanced nutrient uptake, increased flux of been termed nongenomic, appear to be owing to spe- critical ions, and other preparatory changes in the syn- cific recognition of hormone at the cell membrane. thetic machinery of the cell. Because of certain homo- Although the molecular identity of binding site(s) logies of molecular structure, specific receptors for remains elusive and the signal transduction pathways steroid hormones, vitamin D, retinoids, and thyroid require fuller delineation, there is firm evidence that hormone are often considered a receptor superfamily.
    [Show full text]
  • Identification of a Novel Sex Steroid Binding Protein (Receptors/Sterophilin/Chick Oviduct) ROBERT N
    Proc. NatL Acad. Sci. USA Vol. 79, pp. 1742-1746, March 1982 Biochemistry Identification of a novel sex steroid binding protein (receptors/sterophilin/chick oviduct) ROBERT N. TAYLOR* AND RoY G. SMITHt Division of Urology (Surgery), and Department of Biochemistry and Molecular Biology, The University ofTexas Medical School at Houston, Houston, Texas 77030 Communicated by Elwood V. Jensen, November 25, 1981 ABSTRACT We describe a cytoplasmic steroid binding pro- senting the species with the higher affinity. This report de- tein in the chick oviduct which has intriguing characteristics. This scribes the identification of a new estrogen binding protein, protein binds [3H]estradiol with high affinity (Kd = 30 x 10-9 M) designated Z. and limited capacity (300 fmol/mg ofcytosol protein). It sediments at 8 S in low-salt sucrose density gradients and at 4 S in high-salt MATERIALS AND METHODS gradients. Unlike the estrogen receptor, however, this protein also Animals. Two-day-old White Leghorn pullets were pur- binds progesterone, R5020, testosterone, and 5a-dihydrotestos- chased from Texas Animal Specialties (Humble, TX), provided terone with similar affinities and in a competitive manner. More- with food and water ad lib, and raised in a constant temperature over, it is not translocated to the nucleus by the in vivo adminis- environment with a 13/11-hr light/dark schedule. At the chick tration of these sex steroids. The protein is only present in age of1 wk, estrogen stimulation was initiated by subcutaneous estrogen-responsive tissue, and like the sex steroid receptors, its insertion of two silicone implants containing 25 mg of diethyl- synthesis appears to be regulated by estrogen.
    [Show full text]
  • Standardization of Steroid Hormone Assays: Why, How, and When?
    1713 Commentary Standardization of Steroid Hormone Assays: Why, How, and When? Frank Z. Stanczyk,1 Jennifer S. Lee,2 and Richard J. Santen3 1Departments of Obstetrics and Gynecology, and Preventive Medicine, University of Southern California, KeckSchool of Medicine, Women’s and Children’s Hospital, Los Angeles, California; 2Division of Endocrinology, Clinical Nutrition, and Vascular Medicine, Department of Internal Medicine, University of California at Davis, Sacramento, California; and 3Clinical Research, Cancer Center, University of Virginia, Charlottesville, Virginia Abstract Lack of standardization of high-quality steroid hor- lation with biological variables such as body mass mone assays is a major deficiency in epidemiologic index. Similar problems exist with measurements of studies. In postmenopausal women, reported levels of E2 and estrone in men, and estrone and testosterone B serum17 -estradiol (E2) are highly variable and median in women. Interest in mass spectrometry–based assays normal values differ by approximately a 6-fold factor. is increasing as potential gold standard methods with A particular problemis the use of E 2 assays for pre- enhanced sensitivity and specificity; however, these diction of breast cancer risk and osteoporotic fractures, assays require costly instrumentation and highly where assay sensitivity may be the most important trained personnel. Taking all of these issues into con- factor. Identification of women in the lowest categories sideration, we propose establishment of standard pools of E2 levels will likely provide prognostic information of premenopausal, postmenopausal, and male serum, that would not be available in a large group of women and utilization of these for cross-comparison of various in whomE 2 levels are undetectable by less sensitive methods on an international basis.
    [Show full text]
  • Documentation, Codebook, and Frequencies
    Documentation, Codebook, and Frequencies Surplus Sera Laboratory Component: Racial/Ethnic Variation In Sex Steroid Hormone Concentrations Across Age In US Men Survey Years: 1988 to 1991 SAS Export File: SSHORMON.XPT First Published: October 2006 Last revised: N/A NHANES III Data Documentation Laboratory Assessment: Racial/Ethnic Variation in Sex Steroid Hormone Concentrations Across Age In US Men (NHANES III Surplus Sera) Years of Coverage: 1988-1991 First Published: October 2006 Last Revised: N/A Introduction It has been proposed that racial/ethnic variation in prostate cancer incidence may be, in part, due to racial/ethnic variation in sex steroid hormone levels. However, it remains unclear whether in the US population circulating concentrations of sex steroid hormones vary by race/ethnicity. To address this, concentrations of testosterone, sex hormone binding globulin, androstanediol glucuronide (a metabolite of dihydrotestosterone) and estradiol were measured in stored serum specimens from men examined in the morning sample of the first phase of NHANES III (1988-1991). This data file contains results of the testing of 1637 males age 12 or more years who participated in the morning examination of phase 1 of NHANES III and for whom serum was still available in the repository. Data Documentation for each of these four components is given in sections below. I. Testosterone Component Summary Description The androgen testosterone (17β -hydroxyandrostenone) has a molecular weight of 288 daltons. In men, testosterone is synthesized almost exclusively by the Leydig cells of the testes. The secretion of testosterone is regulated by luteinizing hormone (LH), and is subject to negative feedback via the pituitary and hypothalamus.
    [Show full text]
  • Increased Steroid Hormone Dehydroepiandrosterone and Pregnenolone Levels in Post-Mortem Brain Samples of Alcoholics
    Alcohol 52 (2016) 63e70 Contents lists available at ScienceDirect Alcohol journal homepage: http://www.alcoholjournal.org/ Increased steroid hormone dehydroepiandrosterone and pregnenolone levels in post-mortem brain samples of alcoholics Olli Kärkkäinen a,*, Merja R. Häkkinen b, Seppo Auriola b, Hannu Kautiainen c,d, Jari Tiihonen e,f, Markus Storvik a a Pharmacology and Toxicology, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland b Pharmaceutical Chemistry, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland c General Practice, University of Helsinki, FI-00014 Helsinki, Finland d Unit of Primary Health Care, Kuopio University Hospital, FI-70029 Kuopio, Finland e Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, FI-70240 Kuopio, Finland f Clinical Neuroscience, Karolinska Institutet, S-171 76 Stockholm, Sweden article info abstract Article history: Intra-tissue levels of steroid hormones (e.g., dehydroepiandrosterone [DHEA], pregnenolone [PREGN], Received 8 September 2015 and testosterone [T]) may influence the pathological changes seen in neurotransmitter systems of Received in revised form alcoholic brains. Our aim was to compare levels of these steroid hormones between the post-mortem 3 March 2016 brain samples of alcoholics and non-alcoholic controls. We studied steroid levels with quantitative Accepted 4 March 2016 liquid chromatographyetandem mass spectrometry (LC-MS/MS) in post-mortem brain samples of al- coholics (N ¼ 14) and non-alcoholic controls (N ¼ 10). Significant differences were observed between study groups in DHEA and PREGN levels (p values 0.0056 and 0.019, respectively), but not in T levels. Keywords: DHEA Differences between the study groups were most prominent in the nucleus accumbens (NAC), anterior Pregnenolone cingulate cortex (ACC), and anterior insula (AINS).
    [Show full text]