Ernst Schering Research Foundation Workshop

Supplement 1 Molecular and Cellular Endocrinology of the Testis

Ernst Schering Research Foundation Workshop

Editors: Gunter Stock Ursula-F. Habenicht

Vol. 5 Sex Steroids and the Cardiovascular System Editors: P. Ramwell, G. Rubanyi, E. Schillinger

Vol. 6 Transgenic Animals as Model Systems for Human Diseases Editors: E. F. Wagner, F. Theuring

Vol. 7 Basic Mechanisms Controlling Term and Preterm Birth Editors: K. Chwalisz, R. E. Garfield

Vol. 8 Health Care 2010 Editors: C. Bezold, K. Knabner

Vol. 9 Sex Steroids and Bone Editors: R. Ziegler, J. Pfeilschifter, M. Brautigam

Vol. 10 Non-Genotoxic Carcinogenesis Editors: A. Cockburn, L. Smith

Vol. 11 Cell Culture in Pharmaceutical Research Editors: N. E. Fusenig, H. Graf

Supplement 1 Molecular and Cellular Endocrinology of the Testis Editors: G. Verhoeven, U.-F. Habenicht

Ernst Schering Research Foundation Workshop, Supplement 1

Molecular and Cellular Endocrinology of the Testis

G. Verhoeven, U.-F. Habenicht Editors

With 55 Figures

Springer-Verlag Berlin Heidelberg GmbH

ISBN 978-3-662-22191-4 ISBN 978-3-662-22189-1 (eBook) DOI 10.1007/978-3-662-22189-1

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Preface

The European Workshops on Molecular and Cellular Endocrinology of the Testis have become by now a well-established tradition. Thanks to their special format, the quality of the main lectures and miniposters, and the vivid discussions, they enjoy the ever-increasing interest and active participation of all European scientists working in the field. Moreover, since the very beginning they have attracted investigators from all over the world. The most recent "Testis Workshop" was held in De Panne, Belgium, from 27-3\ March, 1994. As always, the frame­work of the workshop was provided by a series of lectures delivered by a panel of internationally recognized authorities. These lectures are ga­thered in the present volume of the Ernst Schering Foundation Work­shop series. Together with the Miniposter book they constitute an excel­lent written account of the Proceedings of the 8th European Testis Workshop.

The testis undoubtedly represents one of the most complex and in­triguing tissues in the body. Both its endocrine function, the secretion of male sex hormones, and its exocrine role, the production of mature spermatozoa, continue to raise startling questions to clinicians, physi­ologists, endocrinologists, and scientists involved in fundamental re­search. Few organs maintain and support a differentiation process as complicated as spermatogenesis; few tissues continually display both mitotic and meiotic cell cyles in such a stringently controlled fashion or a comparable need for coordinated endocrine and local control. As a consequence, the testis has become a preferred model for basic research

VI Preface

on cell differentiation, cell cycle control, environmental and paracrine modulation of cell function, hormone action, signal transduction, and regulation of gene expression. Recent advances in cell isolation cell culture techniques, molecular biology, and genetic techniques such as development of transgenic animals, have found eager applications in research on molecular and cellular endocrinology of the testis. The pre­sent volume offers an elective, but representative, sample of the pro­gress that has been made. A final chapter summarizes the impact that this type of research has had and will have with respect to the clinical diagnosis and treatment of male reproductive dysfunction.

The authors deserve our special thanks not only for delivering excellent state-of-the-art lectures, but also for providing nicely prepa­red manuscripts well before the meeting.

We are also glad to acknowledge the continuous and enthusiastic support and assistance of Focko Rommerts, coorganizer of the mee­ting, of the Permanent Scientific Committee of the Testis Workshops, and of the members of the Local Organinzing Committee as listed be­low.

C. Verhoeven

Permanent Scientific Committee of the European Workshops on Molecular and Cellular Endocrinology of the Testis Brian Cooke, London; Vidar Hansson, Oslo; lIpo Huhtaniemi, Turku; Eberhard Nie­schlag, Munster; Martin Ritzen, Stockholm; Focko F.G. Rommerts, Rotterdam; Jose Saez, Lyon; Mario Stefanini, Rome; Guido Verhoeven, Leuven. Organizing Committee of the 8th European Workshop on Molecular and Cellular Endocrinology of the Testis Guido Verhoeven, Leuven; Walter Heyns. Leuven; Dirk Vanderschueren, Leuven; Ursu­la-F. Habenicht, Berlin; Focko F.G. Rommerts, Rotterdam.

Table of Contents

Hormonal Receptors in the Genital Tract A. Chauchereau. A. Mantel, K. Delabre, M. Misrahi, P. Lescop, M. Perrat-Applanat, H. Loosfelt, M.T. Vu Hai, N. Chinea, C. Meduri, J.-F. Savauret, and E. Milgram . ............... 1

2 Transplantation of Male and Female Germ and Somatic Cells R.C. Casden . ...................................... 15

3 Proliferation and Differentiation of Testicular Interstitial Cells: Aspects of Leydig Cell Development in the (Pre)Pubertal and Adult Testis K.J. Tcerds, MB. Veldhui::en-Tsoerkan, F.F.G. Rommerts, D.C. de Rooij, and JH. Dorrington ..... 37

4 Regulation of the Acute Production of Steroids in Steroidogenic Cells D.M. Stocco and B.J. Clark . .......................... 67

5 Extracellular Matrix Elements, Cell Adhesion Molecules, and Signal Transduction in the Control of Sertoli Cell Function M.D~ ........................................... ~

VIII Table of Contents

6 Interactions Between Androgens, Sertoli Cells and Genn Cells in the Control of Spennatogenesis R.M. Sharpe, C. McKinnell, T. McLaren, M.Millar, T.P. West, S. Maguire, I. Gaughan, V. Syed, B. legou, lB. Kerr, and P.TK Saunders ............................... 115

7 Cell Cycle Checkpoints in Male and Female Genn Cells D.F. Albertini . .................................... 143

8 Signal Transduction in Mammalian Spennatozoa G.S. Kopf, P. Kalab, P. Leclerc, X.P. Ning, D. Pan, and P. Visconti . ............................ 153

9 Diversity and Regulation of cAMP-Dependent Protein Kinases K. Tasken, B.S. Skdlhegg, K.A. Tasken, R. Solberg, F.O. Levy, T. Lea, T. lahnsen, and V. Hansson . .......... 185

10 The Nuclear Respone to cAMP During Spermatogenesis: The Key Role of Transcription Factor CREM P. Sassone-Corsi . ................................. 219

II Transgenic Animals and the Study of Gonadal Function M.M. Matzuk ..................................... 253

12 Clinical Relevance and Irrelevance of Molecular and Cellular Research on the Testis E. Nieschlag ...................................... 273

List of Contributors

Albertini, D.F. Department of Anatomy and Cellular Biology, Tufts University, 136 Harrison Avenue, Boston, MA 02111, USA

Chauchereau, A. Hormones et Reproduction, INSERM Unite 135, 78, rue du General Leclerc, 94275 Le Kremlin Bicetre, France

Clark, B . .T. Department of Biochemistry and Molecular Biology, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA

Delabre. K. Hormones et Reproduction, INSERM Unite 135, 78, rue du General Leclerc, 94275 Le Kremlin Bicetre, France

de Raaij, D.C. Department of Cell Biology, Section of Cell Proliferation and Differentiation, Medical School, Utrecht University, P.O. Box 80.157, 3508 TD Utrecht, The Netherlands

Dorringtoll,l.H. Banting and Best Department of Medical Research, University of Toronto, C.H. Best Institute, 112 College Street, Toronto, Ontario, M5G IL6 Canada

Dvm. M. Department of Cell Biology, Georgetown University Medical Center, :1900 Reservoir Road, NW, Washington, DC 20007, USA

x List of Contributors

Gaughan,l. MRC Reproductive Biology Unit, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9EW, Scotland, UK

Ghinea,N. Hormones et Reproduction, INSERM Unite 135, 78, rue du General Leclerc, 94275 Le Kremlin Bicetre, France

Gosden, R.G. Department of Physiology, University Medical College, Teviot Place, Edinburgh EH8 9AG, UK

Hansson, V. Institute of Medical Biochemistry, University of Oslo, P.O. Box 1112, 0317 Oslo, Norway

lahnsen, T. Institute of Medical Biochemistry, University of Oslo, P.O. Box 1112, 0317 Oslo, Norway

liigou, B. G.E.R.M., Universite de Rennes I, INSERM CJF 91-04, Campus de Baulieu, 35042 Rennes Cedex, France

Kalab, P. Division of Reproductive Biology, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6080, USA

Kerr, lB. Department of Anatomy, Monash University, Clayton, Victoria 3168, Australia

Kopf, G.S. Division of Reproductive Biology, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6080, USA

Lea, T. Institute of Immunology and Rheumatology, The National Hospital, 0027 Oslo, Norway

List of Contributors XI

Leclerc. P. Division of Reproductive Biology, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6080, USA

Lescop, P. Hormones et Reproduction, INSERM Unite 135, n, rue du General Leclerc, 94275 Le Kremlin Bicetre, France

Levy, F.O. Institute of Medical Biochemistry, University of Oslo, P.O. Box 1112, 0317 Oslo, Norway

LoosjClI, H. Hormones et Reproduction, INSERM Unite 135, 78, rue du General Leclerc, 94275 Le Kremlin Bicetre, France

Maguire, S. MRC Reproductive Biology Unit, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9EW, Scotland, UK

Mantel, A.

Hormones et Reproduction, INSERM Unite 135, 78, rue du General Leclerc, 94275 Le Kremlin Bicetre, France

Mal:uk, M.M. Department of Pathology and Institute of Molecular Genetics, Baylor College of Medicine, Houston, Texas 77030, USA

McKinnell, C. MRC Reproductive Biology Unit, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9EW, Scotland, UK

McLaren, T. MRC Reproductive Biology Unit, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9EW, Scotland, UK

Meduri, C. Hormones et Reproduction, INSERM Unite 135, 78, rue du General Leclerc, 94275 Le Kremlin Bicetre, France

XII List of Contributors

Milgram, E. Honnones et Reproduction, INSERM Unite 135, 78, rue du General Leclerc, 94275 Le Kremlin Bicetre, France

Millar,M. MRC Reproductive Biology Unit, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9EW, Scotland, UK

Misrahi,M. Honnones et Reproduction, INSERM Unite 135, 78, rue du General Leclerc, 94275 Le Kremlin Bicetre, France

Nieschlag, E. Institute of Reproductive Medicine of the University (WHO Collaborating Center for Research on Human Reproduction), Steinfurter Str. 107, 48149 MUnster, Gennany

Ning,X.P. Division of Reproductive Biology, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6080, USA

Pan,D. Division of Reproductive Biology, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6080, USA

Perrot-Applanat, M. Hormones et Reproduction, INSERM Unite 135, 78, rue du General Leclerc, 94275 Le Kremlin Bicetre, France

Rommerts, F.F.G. Department of Endocrinology and Reproduction, Medical School, Erasmus University Rotterdam, P.O.Box 1738, 3000 DR Rotterdam, The Netherlands

Sassone-Corsi, P. Laboratoire de Genetique Moleculaire des Eucaryotes, CNRS, Ul84 INSERM, Institut de Chimie Biologique, Faculte de Medecine, II, rue Humann, 67085 Strasbourg, France

List of Contributors

Saullders. P.T.K.

MRC Reproductive Biology Unit, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9EW, Scotland, UK

Sal'lIuret. J.-F.

Hormones et Reproduction, INSERM Unite l35, 7'1'" rue du General Leclerc, 94275 Le Kremlin Bicetre, France

Sharp('. R.M. MRC Reproductive Biology Unit, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9EW, Scotland, UK

Skdlhegg. B.S. Institute of Medical Biochemistry. University of Oslo, P.O. Box 1112, 0317 Oslo, Norway

Solherg. R. Institute of Medical Biochemistry, University of Oslo, P.O. Box 1112, 03 I 7 Oslo, Norway

Sto(,co. D.M.

Department of Biochemistry and Molecular Biology,

XIII

Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA

Syed. V. G.E.R.M .. Universite de Rennes I, INSERM ClF 91-04, Campus de Baulieu. 35042 Rennes Cedex, France

'{askhl. K. Institute of Medical Biochemistry, University of Oslo, P.O. Box 1112, 03 17 Oslo, Norway

Taskcn, K.A. Institute of Medical Biochemistry, University of Oslo, P.O. Box 1112, 03 17 Oslo, Norway

'{('ads. K..T.

Department of Cell Biology and Histology, Faculty of Veterinary Medicine. Utrecht University, P.O.Box 80.157,3508 TD Utrecht, The Netherlands

XIV List of Contributors

Veldhuizen-Tsoerkan, M.B. Department of Cell Biology and Histology, Faculty of Veterinary Medicine, Utrecht University, P.O.Box 80.157, 3508 TD Utrecht, The Netherlands

Visconti, P. Division of Reproductive Biology, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6080, USA

VuHai,M.T. Hormones et Reproduction, INSERM Unite 135, 78, rue du General Leclerc, 94275 Le Kremlin Bicetre, France

West, T.P. MRC Reproductive Biology Unit, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9EW, Scotland, UK