New comprehensive biochemistry vol 18 hormones and their actions part i

HORMONES AND THEIR ACTIONS PART I New Comprehensive Biochemistry Volume 18A General Editors A NEUBERGER London L.L.M van DEENEN Utrecht ELSEVIER Amsterdam - New York Oxford Hormones and their Actions Part I Editors B A COOKE Department of Biochemistry, Royal Free Hospital School of Medicine, University of London, Rowland Hill Street, London NW3 2PF, England R.J.B KING Hormone Biochemistry Department, Imperial Cancer Research Fund Laboratories, P.U Box No 123, Lincoln’s Inn Fields, London WC2A P X , England H.J van der MOLEN Nederlandse Urganisatie voor Zuiver- Wetenschappelijk Onderzoek ( Z W.O ) , Postbus 93138, 2509 A C Den Haag, The Netherlands 1988 ELSEVIER Amsterdam New York Oxford 01988 Elsevier Science Publishers B.V (Biomedical Division) All rights reserved No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior written permission of the Publisher, Elsevier Science Publishers B.V (Biomedical Division), P.O Box 1527 1000 BM Amsterdam, The Netherlands No responsibility is assumed by the Publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the matcrial herein Because of the rapid advances in the medical sciences the Publisher recommends that independent verification of diagnoses and drug dosages should be made Special regulafions for readers in the USA This publication has been registered with the Copyright Clearance Center, Inc (CCC), Salem, Massachusetts Information can be obtained from the C C C about conditions under which the photocopying of parts of this publication may be made in the USA All other copyright questions, including photocopying outside of the USA, should be referred to the Publisher ISBN 0-444-80996-1 (volume) ISBN 0-444-80303-3 (series) Published by: Sole distributors for the USA and Canada: Elsevier Science Publishers B.V (Biomedical Division) P.O Box 211 1000 A E Amsterdam The Netherlands Elsevier Science Publishing Company, Inc 52 Vanderbilt Avenue New York NY 10017 USA Library of Congress Cataloging in Publication Data Hormones and their actions / editors B.A Cooke, R.J.B King, H.J van der Molen p cm (New comprehensive biochemistry; v 18A-) Includes bibliographies and index ISBN 0-444-80996-1 (pt 1) Hormones Physiological effect I Cooke Brian A 11 King, R.J.B (Roger John Benjamin) 111 Molen, H J van der 1V Series: New comprehensive biochemistry; v 18A, etc [DNLM: Hormones-physiology W1 NE372 v 18 / WK 102 H812781 QD415.NJ8 vol 18A etc [ QP57 11 574.19’2 s-dc 19 [ 12’,4051 DN LMiDLC for Library of Congress 88-16501 CIP Printed in The Netherlands V List of contributors M Ascoli, 133 The Population Council, 1230 York Avenue, New York, N Y 10021, U.S.A M.A Blankenstein, 49 Department of Endocrinology, Academic Hospital Utrecht, Utrecht, The Netherlands L Cancela, 269 Division of Biomedical Sciences, University of California, Riverside, C A 92521-0121, U.S.A C.L Clarke, 197 Garvan Institute of Medical Research, St Vincent’s Hospital, Sydney, New South Wales 2010, Australia D.P Edwards, 241 Department of Pathology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, C O 80262, U.S.A U Gehring, 217 Institut f u r Biologische Chemie der Universitat, Im Neuenheimer Feld 501, 6900 Heidelberg, F R G D.N Gower, Division of Biochemistry, United Medical and Dental Schools (Guy’s Hospital), London SEI 9RT, England S.A Haining, 169 Department of Biochemistry, University of Leeds, Leeds LS2 9JT, England B Harper, 169 Department of Biochemistry, University of Leeds, Leeds LS2 9JT, England K.B Horwitz, 241 Departments of Medicine & Pathology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, C O 80262, U.S.A A.S Khanna, 117 Cell Regulation Research Group, Department of Medical Biochemistry, The University of Calgary, Calgary, Alberta, Canada T2N 4N1 R.J.B King, 29 Hormone Biochemistry Department, Imperial Cancer Research Fund, P Box 123, Lincoln’s Inn Fields, London, W C A P X , England N.L Krett, 241 Department of Medicine, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, C O 80262, U S A vi W.I.P Mainwaring, 169 Department of Biochemistry, University of Leeds, Leeds LS2 9JT, England E Mulder, 49 Department of Biochemistry II, Erasmus University, Rotterdam, The Netherlands A.W Norman, 269 Division of Biomedical Sciences, Univecsity of California, Riverside, C A 925214121, U.S.A J Nunez, 61 INSERM U 282, H6pitul Henri Mondor, 51, avenue du Martchal de Lattre de Tassigny, 94010 Crtteil, France M.G Parker, 39 Molecular Endocrinology Laboratory, Imperial Cancer Research Fund, P Box 123, Lincoln’s Inn Fields, London WC2A P X , England L.E Reichert Jr., 105 Department of Biochemistry, Albany Medical College, Albany, N Y 12208, U.S.A D.L Segaloff, 133 The Population Council, 1230 York Avenue, New York, N Y 10021, U.S.A R.L Sutherland, 197 Garvan Institute of Medical Research, St Vincent’s Hospital, Sydney, New South Wales 2010, Australia G Theofan, 269 Division of Biomedical Sciences, University of California, Riverside, C A 925214121, U.S.A T.J Visser, 81 Departments of Internal Medicine 111 and Clinical Endocrinology, Erasmus University Medical School, Rotterdam, The Netherlands D.M Waisman, 117 Cell Regulation Research Group, Department of Medical Biochemistry, The University of Calgary, Calgary, Alberta, Canada T2N 4NI A.E Wakeling, 151 Research Department I , Imperial Chemical Industries PLC, Pharmaceutical Division, Mereside, Alderley Park, Macclesfield, Cheshire S K I 4TG, England C.K.W Watts, 197 Garvan Institute of Medical Research, St Vincent’s Hospital, Sydney, New South Wales 2010, Australia vii Contents List of contributors v Section I General aspects of hormones and hormone actions Chapter The biosynthesis of steroid hormones: an update by D B Cower Introduction Role of lipoproteins in steroidogenesis Mitochondria1 cholesterol 3.1, Transport of cholesterol into mitochondria 3.2 Intramitochondrial transport of cholesterol Side-chain cleavage (SCC) of cholesterol Biosynthesis of corticosteroids 5.1 Enzymes involved in corticosteroid biosynthesis 5.2 1I@-and 18-hydroxylases 5.3 Formation of aldosterone Biosynthesis of the androgens 6.1, Action and properties of 17-hydroxylase and C-17,20-lyase 6.2 Conversion of S-ene-30-hydroxy- to 4-en-3-oxosteroids 6.3 Interconversion of 4-androstenedione and testosterone 6.4 Conversion of testosterone into Sa-dihydrotestosterone (Sa-DHT) Biosynthesis of oestrogens Secretion of synthesized steroid hormones Conclusion Acknowledgements References 4 11 12 13 14 15 17 18 20 20 20 24 25 25 25 Chapter Overview of molecular aspects of steroid hormone actions byR.J.B.King 29 Introduction Intracellular events in steroid action 2.1 Intracellular location of receptors 2.2 Receptor structure 2.3 D N A binding Specificity of steroid action 3.1 Ligand availability 29 29 29 31 31 32 32 viii 3.2 Ligand specificity of receptor 3.3 Agonismiantagonism 3.4 Availability of responsive genes 3.5 Specificity of the steroid response element References 34 35 35 36 37 Chapter Gene regulation by steroid hormones by M.G Parker 39 Introduction Structure and function of steroid receptors Steroid receptor-DNA interactions 3.1 Non-specific D N A binding 3.2 Specific D N A binding Steroid receptor-chromatin interactions Steroid hormone-activated gene networks References 39 39 42 43 43 46 46 47 Chapter Characterization assay and purification of steroid receptors by M A Blankenstein and E Mulder 49 Introduction Properties of steroid receptors 2.1 Binding properties 2.2 Physico-chemical properties Assay of steroid receptors 3.1 General aspects and radioligand assays 3.2 Separation of bound and free ligand 3.3 Immunological assays 3.4 Other steroid receptor assays Purification of steroid receptors 4.1 General protein purification 4.2 DNA-affinity chromatography 4.3 Steroid affinity chromatography 4.4 Immunoaffinity purification Characterization of steroid receptors References 49 50 50 52 53 53 54 54 55 55 55 56 56 57 57 58 Chapter Mechanism of action of thyroid hormone by J Nunez 61 Introduction Thyroid hormone production transport and uptake by the target cells Thyroid hormone nuclear receptors and cellular binding proteins 3.1 Nuclear receptors Induction and repression of pituitary hormones 4.1 Growth hormone 4.2 Thyrotropin Regulation of lipogenesis in the liver 5.1 Malic enzyme 5.2 Fatty acid synthase 61 63 64 65 66 66 68 68 68 70 ix Effects of thyroid hormone on the receptor-adenylate cyclase system in the adipocyte and the hepatocyte The muscle cell: P-adrenergic responsiveness and the expression of myosin heavy chains Thyroid hormones and brain development 8.1, Neuronal differentiation 8.2 Glial cell differentiation Conclusions References 70 72 73 74 75 76 76 Chapter Metabolism of thyroid hormone by T.J Visser 81 Metabolic pathways of thyroid hormone 1.1 Introduction 1.2 Deiodination 1.3 Conjugation Type I iodothyronine deiodinase of liver and kidney 2.1 Properties and distribution 2.2 Substrate specificity 2.3 Inhibitors and affinity labels 2.4 Reaction mechanism 2.5 Cofactor requirements Iodothyronine deiodinases of other tissues 3.1 Type I1 iodothyronine deiodinase 3.2 Type 111 iodothyronine deiodinase 3.3 Possible other iodothyronine deiodinases Transport of iodothyronines into tissues Regulation of thyroid hormone metabolism References 81 81 82 84 85 85 86 87 89 90 93 93 95 96 97 99 100 Chapter Characterization of membrane receptors: some general considerations by L.E Reichert Jr 105 Introduction Preparation of receptor probe Preparation of membrane receptors 3.1 General considerations 3.2 Membranes from cell cultures 3.3 Membranes from tissue homogenates Hormone binding characteristics of the membrane receptor 4.1 Specificity 4.2 Selection of appropriate in vitro system 4.2.1 Effects of time, temperature, buffer 4.2.2 Steady-state (equilibrium) conditions Molecular properties of the membrane receptor Solubilization of the membrane receptor 7.Summary References 105 106 107 107 108 109 111 111 112 112 112 113 114 115 115 280 Non-classical vitamin D responsive systems In the past few years, due to a number of technological improvements, 1,25(OH),D, receptors were able to be identified in a very wide range of tissues and cell lines, extending by far the classical limits of the vitamin D actions upon calcium metabolism (see Ref 2, page 507) In many of these non-classical target tissues, the reason for the presence of 1,25(OH),D, receptors is still under active research We will describe here the possible action of 1,25(OH),D3 in some of those new target tissues in an effort to display the complexity of the vitamin D endocrine system 5.1 The pancreas The involvement of vitamin D in endocrine pancreas function was first suggested by Boquist et al [55], who described 1,25(0H),D3-induced morphological changes compatible with enhanced Pcell activity Accordingly, vitamin D deficiency was shown to inhibit insulin but not glucagon secretion both in vivo and in vitro [56-591, whereas the administration of a maintenance dose of vitamin D, in rats of 2-3 weeks clearly increases insulin release from the isolated perfused pancreas, irrespective of the dietary intake and prevailing levels of serum calcium [60] The existence of high affinity receptors for 1,25(OH),D3 in chick pancreas [61-631, the localization of [3H]1,25(OH)2D3in the nucleus of rat pcells [64] and the presence of pancreasassociated calcium-binding proteins in various species [65-691 suggest that vitamin D or its metabolites may have a direct effect on @cells of pancreas and seem to be essential for the processing of normal insulin secretion Recently, it has been shown that in human patients with vitamin D deficiency, there is impairment of insulin secretion but not glucagon [70], confirming previous results obtained in animals [56-591 This effect is not due to a decrease in the circulating levels of calcium since in these patients the calcemia was normalized through an exogenous intake These first results obtained in humans are important and support the hypothesis of a direct effect of 1,25(OH),D3 upon the pancreatic-P cells 5.2 Reproductive organs In addition to the organs responsible for the development and maintenance of the fetus and newborn, 1,25(OH),D3 receptors have also been localized in several organs from the reproductive apparatus such as the uterus [71], ovary [72] and testis [73] Since these tissues are not directly associated with calcium translocations, the presence of 1,25(OH),D3 receptors may be related to a role of the hormone in cellular proliferation, differentiation and/or maturation Accordingly, the levels of testicular 1,25(OH),D3 receptors have been found to correlate with the meiotic and mitotic development of the spermatogonia [73] Clearly, more studies are needed in this area to clarify the role of the vitamin D hormone in these tissues However, 281 the presence of 1,25(OH),D3 receptors within selected zones of these tissues supports the hypothesis of a specific in situ effect of the hormone 5.3 Neural tissues Receptors for 1,25(OH),D3 have been detected in limited sections of the brain However, the presumed effects of 25(OH),D3 in brain are not well understood Recent data have shown that administration of 1,25(OH),D3 to vitamin D-deficient rats leads to an increase in the activity of the choline acetyltransferase (CAT) in specific brain nuclei [76] The bed nucleus of the stria terminalis and the nucleus centralis of the amygdala are the two regions of the brain in which the highest nuclear concentration of 1,25(OH),D3 has been described [74], and also those reported to have the largest increase in 1,25(0H),D,-stimulated CAT activity [76] These authors have provided the first evidence of a 1,25(0H),D3-dependent activity in brain and therefore suggest that this hormone, like other steroid hormones, may selectively affect the metabolism of a specific neuronal population The presence of vitamin D-dependent calcium-binding proteins (calbindins) in brain has been firmly established However, no vitamin D-dependence has been detected for either the CaBP,,, nor the CaBPgKin brain [76,77] 5.4 Contractile tissues 5.4.1 Skeletal muscle The presence of a muscle weakness or myopathy during metabolic bone diseases was mentioned in one of the first known reports of rickets [78] This fact has been thereafter well documented using clinical and electromyographical as well as histological approaches [79-861, and they have emphasized the satisfactory results obtained during vitamin D therapy These findings have been strengthened by the discovery of a 1,25(OH),D3 receptor in skeletal muscle myoblasts [87,88], as well as by studies showing evidence for a 1,25(OH),D,-dependent mechanism affecting muscle calcium metabolism and muscle contraction [71-741 Furthermore, there is also some evidence tending to link the action of vitamin D metabolites upon muscle calcium fluxes and the maintenance of calcium homeostasis in the whole organism During vitamin D depletion, calcium tends to accumulate in muscle tissue, a quick release occurring after a single administration of vitamin D Apparently, this seems to be directly related with the rapid increase in blood calcium levels [92] However, this effect could also be mediated, at least partially, by PTH [93] In addition, vitamin D seems also to be involved in the regulation of phosphate fluxes across the muscle membranes In this case, 25(OH)D3seems to be the active metabolite, both in vivo and in vitro [94,95] 5.4.2 Cardiac muscle Calcium plays a major role in the function of cardiac muscle [96,97] although the exact mechanisms that mediate the calcium movements in heart remain to be fully elucidated On the other hand, the absolute requirement for calcium of the cardiac muscle cells, together with their marked sensitivity to an excess of circulating calcium levels, indicate their need for a perfect calcium balance The presence of 1,25(OH),D, receptors showing selective localization in a few cardiac muscle nuclei [98] call for an important specific action of the hormone within this very special calcium-dependent organ which may prove to be important in pathological conditions affecting heart function The presence of at least one vitamin D-dependent calcium binding protein in heart [99] suggests that the 1,25(OH),D, receptors are functional and considerably increases its importance In vitro studies using rat ventricular cardiac muscle cells have recently been performed confirming that 1,25(OH),D, does have a direct affect on these cells by stimulating their 45Ca2+uptake and addressing the possibility of a vitamin D-dependent regulation of intracellular calcium homeostasis in heart cells [loo] Further studies in this area promise to be exciting Vitamin D and the immune system In the last few years, considerable evidence has accumulated linking 1,25(OH),D, to the hematopoietic system and possibly to the immune response Non-classical target tissues for 1,25(OH),D,, determined by the presence of 1,25(OH),D3 receptors include thymus and bone marrow, as well as cells derived from these tissues [101-1041 Early studies using a leukemic cell line (HL-60) provided the first line of evidence of the positive effects of 1,25(OH),D3 upon the hematopoietic system In fact, these cells differentiate into macrophage-like cells when submitted to 1,25(OH),D, treatment [lo51 and this finding led to extensive studies of the effects of vitamin D metabolites in different types of cells of hematopoietic origin In addition, macrophages obtained from different tissues can synthesize 1,25(OH),D, [106], a phenomenon previously thought to occur only in kidney cells and the fetoiplacental unit during pregnancy [4,47,48] (see Section 4) Furthermore, pinterferon (yIFN),which is normally produced by activated T-lymphocytes, was found to highly stimulate the 1,25(OH),D, production by macrophages [106] 1,25(OH),D3 being a powerful mediator of the increased calcium levels in the blood stream, these findings were then related to the existence, in some patients, of the so-called hypercalcemia of malignancy, particularly in sarcoidosis since these individuals are known to possess activated T-lymphocytes which secrete large amounts of yIFN Supporting this hypothesis, high levels of 1,25(OH)2D3were detected in some cases of sarcoidosis, once the patient had undergone nephrectomy, thus suppressing the renal synthesis of the hormone [107,108] At this point, the data available strongly support the idea that macrophages may be a normal physiological source of 283 Lymphoid precursor Lymphoblast Pronormoblast Lymphocyte* Prornyelocyte ( Normoblast ** Monocyte b Retlculocyte MARROW -Erythrocyte B L OOD - Macrophage** TISSUE Cells which h a v e been shown t o * P o a r e s s 1.25(OH)20 r e c e p t o r Q Produce 1,25(OHl2D3 Fig Schematic representation of the vitamin D-micro-endocrine system (stem cell differentiation) showing the localization of 1,25(OH)2D3receptors as well as cells which have been shown to synthesize 1,25(OH)D3 1,25(OH),D3, thus providing in situ high levels of the hormone which could be responsible for (1) normal local bone resorption and (2) playing a role in stimulating the differentiation of monocytes along the macrophage pathway (Fig 4) Furthermore, these findings support the hypothesis considering the existence of a local paracrine system for vitamin D, which is depicted in Fig Another line of evidence supporting the linkage between vitamin D and the immune system is derived from the fact that 1,25(OH),D, can suppress immunoglobulin production by activated 284 ANTIGEN T-LY MPHOCYTES CFU-GM GRANULOCY \ I L" OSTEOCLASTS PROLIFERATION W Fig Schematic representation of a possible vitamin D paracrine system in cells from hematopoietic lineage human peripheral blood mononuclear cells [ 1091 Furthermore, 1,25(OH),D, blocks phytohemagglutinin- and antigen-induced lymphocyte blast transformation, possibly through the attenuation of interleukin production [110-1121 In conclusion, the relationship between vitamin D , through its hormonally active form 1,25(OH),D3 and the hematopoietic system and consequently the immune system has been unequivocally established However, much work remains to be done in order to establish the exact role played by 1,25(OH),D, in vivo and its relevance to the treatment of related pathological states Clinical disorders related to vitamin D An increasing number of pathological disorders can be related either directly or indirectly to a wide type of malfunctions affecting one or several of the vitamin D metabolic pathways (Fig 6) These disorders can be roughly related to four different situations: (a) decreased or lack of availability of vitamin D , (b) defective conversion of vitamin D into its major hydroxylated derivatives, (c) altered end-organ responsiveness to the vitamin D metabolites and (d) abnormal interactions between the vitamin D metabolites and other hormones, leading to impaired biological response Because of the complexity of the endocrine and paracrine systems of vitamin D , it is our purpose in this brief review only to outline the different pathologic states resulting from a deficient or altered vitamin D metabolism 285 Osteitis fibrosa cystica Osteomalacia Osteoporosis Osteopenia BLOOD D3 25(OH)D3 lq25(OH)2&, 24R,25(OH&D3 Malabsorption syndrome Sarcoidosis Steatorrhea Vitamin D deficiency remains the most common cause of rickets and osteomalacia in the world, with the exception of the United States and the Scandinavian countries where most dairy products are supplemented with this vitamin This deficiency can be caused either by dietary habits or by insufficient exposure to ultraviolet light The same type of symptoms can be observed when there is interruption of the normal vitamin D metabolic pathways due to a number of liver and/or kidney diseases In addition, a number of inherited factors can lead to different types of vitamin D resistance which require massive supplements of vitamin D and/or minerals Extensive reviews have been published depicting both the clinical features and their most likely causes, as well as the possible treatments of the different types of clinical disorders resulting from vitamin D deficiencies [ 113-1 171 The newly defined role for 1,25(OH),D3 upon the hematopoietic system could also have clinical relevance in bone disorders such as osteoporosis where patients have been shown to possess abnormal T-cell subsets [ 1181 Summary Vitamin D is now clearly considered to be a pro-hormone Its principal hormonally active derivative, 1,25(OH),D,, acts at the genomic level following the same path- 286 way previously described for other more classical steroid hormones In addition, there is clear evidence for 1,25(OH)*D3being involved in a different type of receptor-mediated action not requiring genomic activation Furthermore, both in vivo and in vitro data suggest that this pluripotent seco-steroid hormone is not only a major regulator of the mineral metabolism and calcium homeostasis, but is also involved in a number of other biological activities not yet fully understood but clearly related to cell proliferation and differentiation The number of tissues and cell types possessing receptors for vitamin D derivatives has been greatly increased in the last few years New target tissues including the heart, pancreas, ovary, testis, lung, as well as a possible involvement within the immunological response, bring forward a whole new aspect of the vitamin D endocrine and paracrine system which promise to lead to new and very exciting findings in the near future 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Dunnigan, M.G., McIntosh, W.B Ford J A , et al (1982) In: Calcium Disorders (Heath, D A and Marx, S.J eds.) pp 125-150 Butterworth Scientific, London 116 Liberman V.A., Samuel, R., Halabe, A., Kauli, R Edelstein, S , Weisman Y ,Papapoulos, W.E Clemens, T.L., Fraher L.J and O’Riordan J L (1980) Lancet i, 504-507 117 Fournier, A , Sebert, J.L., Boudailliez, B and Moriniere P (1985) Ann Med Interne (Fr) 136, 4179 118 Fujita T., Matsui T., Nakao, Y and Watanahe, S (1984) Min Electrol Metab 10 375-378 This Page Intentionally Left Blank 29 Subject Index Accessory sexual glands, androgens 190 Action of androgens, 171 antioestrogens, 35, 161, 210 glucocorticoids, 217 LHRH, 152 oestrogens, 197 progesterone, 241 steroid hormones, 29, 30, 39, 169, 197, 217, 24 thyroid hormones, 61, 66 Adenylate cyclase, thyroid hormones, 70 Aldosterone, biosynthesis, 14 Anabolic steroids, 183 Androgens, accessory sexual glands, 190 anterior pituitary, 188 biological actions, 171 biosynthesis, 15 bone, 190 breast, 188 central nervous system 186 gene expression, 193 haemopoietic organs, 177 hair, 188 kidney, 179 lymphocytic organs, 190 muscle, 182 salivary glands, 178 skin, 189 testis, 174 urogenital tract, 175 Antagonists to steroid hormones, 35, 156 Anterior pituitary, androgens, 188 Antiandrogens, 160, 192 Antioestrogens, 161, 210 Biosynthesis of aldosterone, 14 androgens, 15 corticosteroids, 11 oestrogens, 20 peptide hormones, 118 steroid hormones, thyroid hormones, 63 vitamin D , 269 Bone, androgens, 190 vitamin D , 277 Brain development, thyroid hormones, 73 Breast, androgens, 188 oestrogens, 60, 153, 208, 242 progesterone, 242 Calcium, vitamin D, 274 Cell proliferation, oestrogen, 207 Central nervous system, androgens, 186 Cholesterol, side chain cleavage, transport, Clinical disorders, vitamin D, 284 Conjugation, thyroid hormones, 84 Contractile tissues, vitamin D , 281 Corticosteroids, biosynthesis, 11 DNA binding of androgens, 193 glucocorticoids, 222, 226, 230 oestrogen, 203 progesterone, 258 steroid hormones, 31, 42, 46 FSH receptors, 105 Gene expression, androgens, 193 oestrogen, 205 glucocorticoids, 229 progesterone, 257 steroid hormones, 39 GH, thyroid hormones, 66 Glial cell differentiation, thyroid hormones, 75 Glucocorticoids, biological actions, 217 DNA binding, 222, 226 230 gene activation, 229 lymphocytolysis, 217 292 receptor M,, 233 receptor defects, 220 receptors, 221 Haemopoietic organs, androgens, 177 Hair, androgens, 188 Immune system, vitamin D, 282 Internalization, peptide hormones, 129, 134, 140 Intestine, vitamin D , 277 Iodination peptide hormones, 106 Iodothyronine deiodinases 93 Kidney, androgens, 179 vitamin D , 276 LHRH, action, 152 analogues, 154 Lipoproteins, Lipogenesis, thyroid hormones, 68 Lymphocytic organs, androgens, 190 Lymphocytolysis, glucocorticoids 217 Membrane receptors, characterization 112 isolation, 107 solubilization, 114 specificity, 1 Mineral hemostasis, vitamin D , 276 Muscle, androgens, 182 thyroid hormones, 72 Neural tissues, vitamin D , 281 Neuronal differentiation, thyroid hormones, 74 Oestrogen, actions, 197 biosynthesis, 20 breast, 60, 153, 208 cell proliferation, 207 D N A binding, 203 gene expression, 205 receptor, 200 receptor genes, 203 Pancreas, vitamin D , 280 Peptide hormones, biosynthesis, 118 circulation, 128 degradation, 128 identity, I18 internalization, 129 134 internalization, temperature effects, 140 iodination, 106 prohormones, 121 receptor down regulation 146 receptors microaggregation, 144 recycling, 136 release, 127 storage, 127 Progesterone, action, 241 DNA binding, 258 gene expression, 257 reccptors, 243 receptor phosphorylation, 254 receptor localization, 255 receptor structure, 245 Prohormones, peptide hormones, 121 Receptor assay steroid hormones 50, 53 characterization, steroid hormones, 57 defects, glucocorticoids, 220 down regulation peptide hormones, 146 glucocorticoids, 221 localization, progesterone, 255 microaggregation, peptide hormones, 144 phosphorylation, progesterone, 254 progesterone, 243 properties, steroid hormones, 52 purification steroid hormones, 55 recycling, peptide hormones, 136 specificity, 34 steroid hormones, 30 structure steroid hormones, 31, 39 structure, progesterone, 245 thyroid hormones, 64 vitamin D, 271 Reproduction, vitamin D , 278, 280 Salivary glands, androgens, 178 Skin, androgens, 189 Solubilization, membrane receptors, 114 Specificity, membrane receptors, 11 steroid hormones, 32, 36 293 Stereochemistry, testosterone, 173 Steroid hormones, action, 29, 30, 39, 169, 197, 217, 241 antagonists, 36, 156 biosynthesis, DNA binding, 31, 42, 46 gene regulation, 39 receptor structure, 39 receptor characterization, 57 receptor assay, 50, 53 receptor properties, 52 receptor purification, 55 receptors, 30 secretion, 24 specificity, 32 Testis, androgens, 174 Testosterone, active metabolites, 170 stereochemistry, 173 Thyroid hormones, action, 61, 66 adenylate cyclase, 70 biosynthesis, 63 brain development, 73 cofactors for metabolism, 90 conjugation, 84 GH, 66 glial cell differentiation, 75 inhibitors of metabolism, 87 lipogenesis, 68 mechanisms of metabolism, 89 metabolism, 81 muscle, 72 neuronal differentiation, 74 receptors, 64 regulation of metabolism, 99 structures, 62 transport, 63, 97 TSH, 68 TSH, thyroid hormones, 68 Urogenital tract, androgens, 175 Vitamin D, biosynthesis and metabolism, 269 bone, 277 calcium, 274 clinical disorders, 284 contractile tissues, 281 endocrine system, 270 immune system, 282 intestine, 277 kidney, 276 mineral hemostasis, 276 neural tissues, 281 pancreas, 280 receptor, 271 reproduction, 278, 280 This Page Intentionally Left Blank ... microfilaments by causing their cross-linking and polymerization, is cytochalasin B Treatment of adrenal and ovarian cells with this caused rapid and reversible inhibition of trophic hormone-induced... consisting of protein (apolipoprotein) and lipids and, depending on their hydrated densities, are classified as follows: chylomicra, very low density lipoproteins (VLDL), intermediate density lipoproteins... (eds.) Hormones and their Acrions Purr 01988 Elsevier Science Publishers BV (Biomedicd Division) CHAPTER The biosynthesis of steroid hormones: an up-date D.B GOWER Division of Biochemistry, United