STEROIDS - FROM PHYSIOLOGY TO CLINICAL MEDICINE Edited by Sergej M. Ostojic Steroids - From Physiology to Clinical Medicine http://dx.doi.org/10.5772/46119 Edited by Sergej M. Ostojic Contributors Dai Mitsushima, Hajime Ueshiba, Rosário Monteiro, Cidália Pereira, Maria João Martins, Paul Dawson, Zulma Tatiana Ruiz-Cortés, Anna Kokavec, Seung-Yup Ku, Sanghoon Lee, Marko D Stojanovic, Sergej Ostojic, Emad Al-Dujaili Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2012 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Ana Pantar Technical Editor InTech DTP team Cover InTech Design team First published November, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from [email protected] Steroids - From Physiology to Clinical Medicine, Edited by Sergej M. Ostojic p. cm. ISBN 978-953-51-0857-3 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface VII Section 1 Physiology and Pathophysiology of Steroids 1 Chapter 1 Gonadal Sex Steroids: Production, Action and Interactions in Mammals 3 Zulma Tatiana Ruiz-Cortés Chapter 2 The Biological Roles of Steroid Sulfonation 45 Paul Anthony Dawson Chapter 3 Hippocampal Function and Gonadal Steroids 65 Dai Mitsushima Chapter 4 11β-Hydroxysteroid Dehydrogenases in the Regulation of Tissue Glucocorticoid Availability 83 Cidália Pereira, Rosário Monteiro, Miguel Constância and Maria João Martins Section 2 Steroids: Clinical Application 107 Chapter 5 Sex Steroid Production from Cryopreserved and Reimplanted Ovarian Tissue 109 Sanghoon Lee and Seung-Yup Ku Chapter 6 Female Salivary Testosterone: Measurement, Challenges and Applications 129 E.A.S. Al-DujailI and M.A. Sharp Chapter 7 Limits of Anabolic Steroids Application in Sport and Exercise 169 Marko D. Stojanovic and Sergej M. Ostojic VI Contents Chapter 8 Steroidogenic Enzyme 17,20-Lyase Activity in Cortisolsecreting and Non-Functioning Adrenocortical Adenomas 187 Hajime Ueshiba Chapter 9 Salivary or Serum Cortisol: Possible Implications for Alcohol Research 199 Anna Kokavec Preface Understanding complex mechanisms of action and key roles in different biological processes in the body has moved steroid science and medicine to expand rapidly in the past decades. Dozens of distinct steroids are identified as both control and target molecules, with regulation of physiological and pathophysiological steroidogenesis recognized as one of the essential research topics in the field. On the other hand, steroids have been practiced as both medical agents and clinical markers for many purposes, from bone marrow stimulation to growth monitoring. This book covers contemporary basic science on steroid research, along with steroid practical application in endocrinology and clinical medicine. The book is divided in two parts. The first part deals with physiological and pathophysiological roles of steroids, with reference to production and action of gonadal steroids, role of steroid sulfonation in mammalian growth and development, sex specific and steroids-dependent mechanism of hippocampal function, and the importance of hydroxysteroid dehydrogenases for the modulation of tissue glucocorticoid availability. The second part will cover different aspects of steroids application in clinical environment. Topics covered in the second part include the endocrine function after ovarian transplantation in terms of sex steroid production from the cryopreserved and reimplanted ovaries, the diagnostic significance of collection, storage and measurement of androgens in saliva of females, main drawbacks of steroids use in sport and exercise, analysis of serum steroid hormone profiles in patients with adrenocortical tumors, and correlation between salivary and serum cortisol responses after alcohol intake. In response to the need to address novel and valuable information on steroids science and medicine, we sincerely hope that this book will enable readers to comprehend this fast- growing and exciting scientific field. Sergej M. Ostojic, MD, PhD Professor of Biomedical Sciences in Sport & Exercise Center for Health, Exercise and Sport Sciences, Belgrade Faculty of Sport and Physical Education, University of Novi Sad Serbia Section 1 Physiology and Pathophysiology of Steroids Chapter 1 Gonadal Sex Steroids: Production, Action and Interactions in Mammals Zulma Tatiana Ruiz-Cortés Additional information is available at the end of the chapter http://dx.doi.org/10.5772/52994 1. Introduction There are five major classes of steroid hormones: testosterone (androgen), estradiol (estro‐ gen), progesterone (progestin), cortisol/corticosterone (glucocorticoid), and aldosterone (mineralocorticoids). Testosterone and its more potent metabolite dihydrotestosterone (DHT), progesterone and estradiol are classified as sex-steroids, whereas cortisol/corticoster‐ one and aldosterone are collectively referred to as corticosteroids. Sex steroids are crucial hormones for the proper development and function of the body; they regulate sexual differentiation, the secondary sex characteristics, and sexual behavior pat‐ terns. Sex hormones production is sexually dimorphic, and involves differences not only in hormonal action but also in regulation and temporal patterns of production. Gonadal sex ste‐ roids effects are mediated by slow genomic mechanisms through nuclear receptors as well as by fast nongenomic mechanisms through membrane-associated receptors and signaling cas‐ cades. The term sex steroids is nearly always synonymous with sex hormones (Wikipedia). Steroid hormones in mammals regulate diverse physiological functions such as reproduc‐ tion, mainly by the hypothalamic-pituitary-gonadal axis, blood salt balance, maintenance of secondary sexual characteristics, response to stress, neuronal function and various metabolic processes(fat, muscle, bone mass). The panoply of effects, regulations and interactions of go‐ nadal sex steroids in mammals is in part discussed in this chapter. 2. Production of gonadal steroids Cholesterol is found only in animals; it is not found in plants although they can produce phytoestrogens from cholesterol-like compounds called phytosterols. © 2012 Ruiz-Cortés; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 4 Steroids - From Physiology to Clinical Medicine Because cholesterol cannot be dissolved in the blood, it must be carried through the body on a "carrier" known as a lipoprotein. A lipoprotein is cholesterol covered by protein. There are two types of liproproteins-LDL (low density lipoprotein) and HDL (high density lipopro‐ tein). All steroid hormones are synthesized from cholesterol through a common precursor steroid, pregnenolone, which is formed by the enzymatic cleavage of a 6-carbon side-chain of the 27- carbon cholesterol molecule, a reaction catalyzed by the cytochrome P450 side- chain cleavage enzyme (P450scc, CYP11A1) at the mitochondria level (Figure 1a). The ovari‐ an granulosa cells mainly secrete progesterone (P4) and estradiol (E2); ovarian theca cells predominantly synthesize androgens,and ovarian luteal cells secrete P4 (and its metabolite 20α-hydroxyprogesterone (Hu et al., 2010). Progesterone is also synthesized by the corpus luteum and by the placenta in many species as it will be mentioned later. Testicular Leydig cells are the site of testosterone (T) production. The brain also synthesizes steroids de novo from cholesterol through mechanisms that are at least partly independent of peripheral ster‐ oidogenic cells. Such de novo synthesized brain steroids are commonly referred to as neuro‐ steroids. In mammals, the adrenal or suprarrenal glands are endocrine glands that produce at the outer adrenal cortex androgens such as androstenedione. All these steroidogenic tissues and cells have the potential to obtain cholesterol for steroid synthesis from at least four potential sources: a) cholesterol synthesized de novo from ace‐ tate;b) cholesterol obtained from plasma low-density lipoprotein (LDL) and high-density lipoprotein (HDL); c) cholesterol-derived from the hydrolysis of stored cholesterol esters in the form of lipid droplets; and d) cholesterol interiorized from the plasma membrane, all this mechanisms implicating cell