STEROIDS – BASIC SCIENCE Edited by Hassan Abduljabbar Steroids – Basic Science Edited by Hassan Abduljabbar Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 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. As for readers, this license allows users to download, copy and build upon published chapters 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. 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 Bojan Rafaj Technical Editor Teodora Smiljanic Cover Designer InTech Design Team Image Copyright loriklaszlo, 2011. DepositPhotos First published December, 2011 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Steroids – Basic Science, Edited by Hassan Abduljabbar p. cm. ISBN 978-953-307-866-3 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Part 1 Physiology of Steroid Hormones 1 Chapter 1 Hormonal and Neural Mechanisms Regulating Hormone Steroids Secretion 3 Roberto Domínguez, Angélica Flores and Sara E. Cruz-Morales Chapter 2 The Tissue Specific Role of Estrogen and Progesterone in Human Endometrium and Mammary Gland 35 Karin Tamm, Marina Suhorutshenko, Miia Rõõm, Jaak Simm and Madis Metsis Chapter 3 Evolving Trends in Estrogen Receptor Biology 65 Raghava Varman Thampan Part 2 Pathophysiology of Steroid Hormones 83 Chapter 4 Cryptorchidism and Steroid Hormones 85 Marzena Kamieniczna , Anna Havrylyuk and Maciej Kurpisz Chapter 5 Dehydroepiandrosterone in Nonalcoholic Fatty Liver Disease 97 Yoshio Sumida, Kyoko Sakai, Tomoyuki Ohno, Kazuyuki Kanemasa, Yutaka Inada, Naohisa Yoshida, Kohichiroh Yasui, Yoshito Itoh, Yuji Naito, Toshikazu Yoshikawa Chapter 6 DHEA and Impaired Glucose Tolerance Clinical and Basic Study 109 Hajime Ueshiba Chapter 7 17-Hydroxysteroid Dehydrogenase Type 3 Deficiency: Diagnosis, Phenotypic Variability and Molecular Findings 119 Maria Felicia Faienza and Luciano Cavallo VI Contents Chapter 8 Steroid Hormones in Drosophila: How Ecdysone Coordinates Developmental Signalling with Cell Growth and Division 141 Leonie Quinn, Jane Lin, Nicola Cranna, Jue Er Amanda Lee, Naomi Mitchell and Ross Hannan Part 3 Pharmacology 169 Chapter 9 Approaches for Searching of Modified Steroid Estrogen Analogues with Improved Biological Properties 171 Alexander Shavva, Svetlana Morozkina and Olga Galkina Chapter 10 Drug Design Approaches to Manipulate the Agonist-Antagonist Equilibrium in Steroid Receptors 221 Scott J. Lusher, Paolo Conti, Wim Dokter, Pedro H. Hermkens and Jacob de Vlieg Preface This book explains the basic science of steroids and is targeted towards professionals engaged in health services. It should be noted that medical science evolves rapidly and some information like the understanding of steroids and their therapeutic use may change with new concepts quickly. Steroids are either naturally occurring or synthetic fat-soluble organic compounds. They are found in plants, animals, and fungi. They mediate a very diverse set of biological responses. The most widespread steroid in the body is cholesterol, an essential component of cell membranes, and the starting point for the synthesis of other steroids. Since the science of steroids has an enormous scope, we decided to put the clinical aspects of steroids in a different book titled “Steroids: Clinical Aspects”. The two books complete each other. We hope that the reader will gain valuable information from both books and enrich their knowledge about this fascinating topic. Hassan Abduljabbar Professor of Obstetrics and Gynecology, King Abdulaziz University, Kingdom of Saudi Arabia [...]... (3β-HSDs) are located at the microsomal fraction, and are expressed in the adrenal cortex and in steroidogenic cells of the 6 Steroids – Basic Science gonads The expression of 3β-HSDs is enhanced by ACTH and LH These isomerases catalyze the formation of Δ4-3-ketosteroids from A5-3β-hydroxysteroids, an obligate step in the biosynthesis of progestins, androgens, estrogens, mineralocorticoids and glucocorticoids... two neuropeptides produced by neurones located in the lateral hypothalamus Orexins A and B bind to two different receptors that are coupled to G proteins Both neuropeptides raise basal corticosterone secretion by dispersed cells obtained from the rat’s fasciculate-reticular zone, and do not affect either maximally 10 Steroids – Basic Science ACTH stimulated corticosterone production by cells of the... 2006), and participate in the regulation of appetite and metabolic processes Experimental studies show that some adipokines play a role regulating steroid hormones secretion by different organs 8 Steroids – Basic Science 5.2.1 Leptin Leptin is a hormone secreted by the adipose tissue, and its participation in the regulation of steroid hormones is controversial In vitro studies show that the participation... Based on its functional actions, steroid hormones are classified into five principal classes: estrogens (estradiol, estrone, estriol), progestins (progesterone), androgens (testosterone, A4, 4 Steroids – Basic Science dihydrotestosterone), glucocorticoid (cortisol, corticosterone), and mineralocorticoids (aldosterone, deoxicorticosterone) All steroid hormones derive from cholesterol in a process that... the inner mitochondrial membrane (Manna et al., 2001) In cultivated Leydig cells, T3 treatment increased testosterone and estradiol secretions in a dose dependent manner (Maran et al., 2000) 12 Steroids – Basic Science 5.7 Protein kinases and cAMP Protein kinases (PKs) are a group of enzymes that modify other enzymes by adding phosphate groups (phosphorylation), which changes the enzyme’s activity PKs... innervation modulates the response to ACTH The effects are related to functional changes in the adrenal medulla and do not depend on the sensitive of the afferent fibers (Ulrich-Lai et al., 2006) 14 Steroids – Basic Science The ovaries receive motor innervations from the sympathetic and the parasympathetic system via the vagus nerve, and possess afferent fibers travelling sympathetic and vagal routes (Burden... resulted in lower release of androstenedione in systems obtained from rats on diestrus 1, and higher release of androstenedione in systems obtained from rats on diestrus 2 (Bronzi et al., 2011) 16 Steroids – Basic Science The results presented above suggest that the adrenergic activation of the CG plays a role in regulating ovarian androgen secretion, and that this role varies along the estrous cycle Therefore,... multisynaptic neural pathway between the abdominal wall, the adrenals and the ovaries, a pathway that is mediated through the innervations of the adrenals and ovaries (Flores et al., 2008) 18 Steroids – Basic Science Fig 2 Comparative effects of ventral or dorsal sectioning the abdominal wall on progesterone, testosterone, and estradiol serum levels Based in data published by Flores et al., (2008)... resulted in higher progesterone levels While extirpating the left ovary eliminated the progesterone levels increase, extirpating the right ovary did not Regardless of the day of the estrus cycle 20 Steroids – Basic Science Testosterone Progesterone 90 * 80 * 80 400 350 300 250 200 90 350 250 100 Right 400 Right 100 Left 300 Left 200 70 70 60 60 50 50 40 40 150 150 30 30 100 100 20 20 10 10 50 50 0 0 D1 Sugery... higher ovulation rates, compensatory ovarian hypertrophy, and number of ova shed; while the same procedure to left ULO rats (right ovary in-situ) resulted in a decrease of the same parameters 22 Steroids – Basic Science 160 140 120 100 80 60 40 20 0 # * * # PROGESTERONE * TESTOSTERONE ESTRADIOL ABDOMINAL WALL SURGERY LEFT SON STIMULATION LEFT SON SECTION RIGHT SON STIMULATION RIGHT SON SECTION * p . STEROIDS – BASIC SCIENCE Edited by Hassan Abduljabbar Steroids – Basic Science Edited by Hassan Abduljabbar Published. of the Steroids – Basic Science 6 gonads. The expression of 3β-HSDs is enhanced by ACTH and LH. These isomerases catalyze the formation of Δ4-3-ketosteroids from A5-3β-hydroxysteroids,. the synthesis of other steroids. Since the science of steroids has an enormous scope, we decided to put the clinical aspects of steroids in a different book titled Steroids: Clinical Aspects”.