Skinner, Michael K

English

Washington State University  institutional repository

I 16 Cell-Cell Interactions in the Testis Which Regulate Gonadal Function Michael K. Skinner Department of Pharmacology, Vanderbilt University, Nashville, Tennessee he interactions between different cell types became essential for survival with the evolution of multicellular organisms. The cell-cell interactions that have evolved are important for embryogenesis, organogenesis, and the maintenance of cellular function, growth, and differentiation. A large number of different types of cell-cell interactions have evolved and been previously categorized into environmental, nutritional, and regulatory interactions (1). Envi­ronmental interactions are mediated via extracellular matrix and cell adhesion components and are important for the structural differentiation ofa cell and tissue. Nutritional interactions are those involving the transport of essential components and metabolites between cells needed for cell survival. Regulatory interactions are mediated by paracrine/autocrine factors via a signal transduction event to influence cellular function on a molecular level. Although the molecular mechanisms and functions of these three categories of interaction are distinct, all three types of interaction are essential. The testis provides an efficient model system to investi­gate cell-cell interactions. Observations can lead to an understanding of male reproduction and testis function, as well as provide insight into general cell-cell interactions which can occur in many different organs. Th.is chapter will summarize several cell-cell interactions that influence testis function and that relate to the neuroendocrine regulation of male reproduction. CELL-CELL INTERACTIONS The primary cell types in the testis are the Leydig cells, peritubular myoid cells, Sertoli cells, and the germinal cells. The Sertoli cells form the seminiferous tubule and provide the micro-environment and cytoarchitectural support for the develop­ing germinal cells. The peritubular myoid cells surround and form the exterior wall of the tubule. The Leydig cells are in the interstitium and are the site for the production of androgens. Neuroendocrine regulation of the pituitary indirectly regulates testis function through alterations in gonadotropin levels. Luteinizing 175 176 M. K. Skinner LH <tl)Leydigi Peri tubular FSH Fig. 1. An illustration of the major cell-cell interactions in the testis. This will likely be the first of many important cell-cell interactions yet to be identified. See the text for discussion. hormone (LH) acts on the Leydig cells to stimulate androgen production which maintains the process of spermatogenesis. Androgens also feed back on the pituitary to alter gonadotropin production. Follicle stimulating hormone (FSH) •acts directly on the Sertoli cell to promote and maintain cellular differentiation. This endocrine regulation of testis function is critical for the maintenance of male reproduction; however, local cell-cell interactions have also been found to have an important role in testis physiology. Environmental interactions occur primarily between Sertoli cells and ger­minal cells as well as Sertoli cells and peritubular cells. The complex morphology and structural support that the Sertoli cells provide the developing germinal cells comprise a classic example of an environmental interaction. This elegant cytoarchitecture is essential to maintain the proper morphology of the germ cells. This environmental interaction between Sertoli cells and germ cells is critical for the process of spermatogenesis. To help maintain the structural integrity of the seminiferous tubule, a complex extracellular matrix is formed between Sertoli cells and peritubular cells. Both cell types cooperate in the production of indi..,idual components of this basement membrane (2), and this matrix has been shown to he important for the structural differentiation of Sertoli cells (3). Although th1:­environmental interaction between peritubular cells and Sertoli cells is important for maintaining the structural differentiation and integrity of the tubule. this extracellular matrix does not appear to regulate Sertoli cell function on a molecular level (4). Nutntwnal interactions occur primarily between Sertoli cells and germrn:d cells, due to the formation of the blood-testis barrier by Sertoli cells. Essent1:d components from the circulatory system can be obtained by Leydig cells. perituhu­lar cells. and Sertoli cells. but they cannot traverse the blood-testis barrier for th,, developing gem1inal cells. Therefore. these essential components and met~1bolit1< -177 Cell-Cell Interactions In the Testis Which Regulate Gonadal Function must be transported through or synthesized by the Sertoli cell. A number of tranSport proteins are synthesized by Sertoli cells which carry metals, vitamins, and lipids to the developing germ cells ( 1). Sertoli cells also produce and secrete several energy metabolities, such as lactate and pyruvate, which are utilized by the developing germ cells. Therefore, the micro-environment created within the semi­niferous tubule is essential for the process of spennatogenesis. Regulatory interactions are possible between all the different cell types in the testis and can be mediated by a wide variety ofparacrine and autocrine factors. The ability of the seminiferous tubule to influence Leydig cell androgen production has been shown with a number ofin vitro experiments; however, the specific factors involved remain to be investigated. In addition, the level of androgen production by Leydig cells is nearly an order of magnitude higher than required for the mainte­nance of spermatogenesis in the adult. Therefore, small alterations in androgen production would not 3ppear to be important for the maintenance of testis function. The apparent paradox may be resolved with the future identification of alternate potentially important secretory products of Leydig cells. Regulatory interactions between Sertoli cells 3nd germinal cells have also been postulated; however, the factors involved remain to be identified and characterized. Whether the Sertoli cell­germ cell interactions requi red to maintain the process of spermatogenesis utilize a passive process involnng primarily nutritional interactions or an active process involving a complex network of regulatory interactions remains to be elucidated. Interactions between peritubular cells and Sertoli cells have been demon­strated with the 1dentific3tion of a nonmitogenic paracrine factor that is produced by peritubular cells. modulates Sertoli cell function, and is termed P-Mod-S (5). P­Mod-S has been puntied 3nd shown to have a more dramatic effect on Sertoli cell function than an md1\·1dual re1-,'l.llatory agent previously identified, including FSH (6). The ability of P-.\lod-S to have such a dramatic effect onSertoli cell function is in part due to its unique signal transduction system involving cGMP (7). This paracrine factor 1s pn,;tulated to have an important role in the maintenance and control of testis furn.:t1on. The production of P-'.\fod-S by peritubular cells is regulat­ed by androgens ,5 ,. Therefore, peritubular cell-Sertoli cell interactions mediated via P-Mod-S pro\ idea potentially important mode of androgen action in the testis. Sertoli cells generally have negligible response to androgens in vitro, but the presence of peritububr cells augments the apparent actions of androgens on Sertoli cells (8). Due to the Jr:m1atic effects of P-.\fod-S on Sertoli cell differentiation, this regulatory int('ractlon between peritubular cells and Sertoli cells is postulated to provide a major mode uf androgen action in the testis. P-Mod-S generally stimulates most Sertoli cell functions 16). Recently, P-.\fod-S has also been found to stimulate inhibin productwn ln :-,;crtoli cells (9). Androgens have previously been shown to have negligible df,ct,. ,1n 1nlubin production by Sertoli cells in vitro; therefore, the ability of P-.\Iod-:-,; •,1 Tc.,'Ulate inhibin production provides a mechanism for andro­gens to regulate lflH11n il'vels in ,ivo. This indirect effect of the endocrine system on inhibin product:, -ri un In tum feed back to and regulate the endocrine system. Other t ,,.•,,r~ lft\nhed 1n pentubular cell-Sertoli cell inter3ctions include tran,,ti,rn'.:,!_: .:!·,,·.\th bctor-ct ,TGF-c£) and transforming growth factor-0 178 M. K. Skinner (TGF-!3). Both peritubular cells and Sertoli cells produce the epidermal growth factor (EGF)-like peptide TGF-0. and the growth inhibitor TGF-13 (10, 11). The TGF-a and TGF-13 produced bySertoli cells can act as paracrine factors to influence peritubular cell growth (10) and differentiation (11), respectively. Sertoli cells do not appear to contain the EGF receptor, so they may not be a site ofTGF-a action. TGF-13, however, may influence Sertoli cell functions. Therefore, the peritubular cell-Sertoli cell interaction mediated via TGF-a and TGF-13 may be an important regulatory interaction in the testis to regulate testis growth and differentiation. SUMMARY Analysis of cell-cell interactions in the testis has developed a better understanding of the factors involved in the maintenance of testis physiology, as well as providing insight into the general cellular interactions present in essentially all tissues. As an example, the information regarding peritubular cell-Bertoli cell interactions medi­ated via P-Mod-S provides the first biochemical evidence for the hypothesis that mesenchymal cells influence epithelial cell function through the production of mesenchymally derived inducer substances. The environmental, nutritional, and regulatory interactions identified will all be important for the regulation of gonadal function. The ability of the endocrine system to influence these cell-cell interactions provides an efficient mechanism for a local control of testis function. This observa­tion indicates how important an understanding oflocal cell-cell interactions is to the complete understanding of the actions of the endocrine system. The regulation of male reproductive biology by the neuroendocrine system appears to result in the initiation of a cascade of events that result in an influence on cell-cell interaction in the testis. Subsequently, these cell-cell interactions in the testis can feed back on the endocrine system through agents such as inhibin. Therefore, elucidation of the neuroendocrine regulation of reproduction will require further investigation of the local regulation of gonadal function. REFERENCES 1. Skinner .\1K Ann ~"Y Acad Sci 1987;513:158. 2. Skinner '.\fK. Tung PS, Fritz IB. J Cell Biol 1985; 100: 1941. 3. Hadley .\U. Byers SW, Suarez-Quian CA, Kleinman HK, Dym :\1. ,J Cell Bi,ii 1985;1011511. 4. Anthony CT. Skinner '.\1K. Biol Reprod 1989:40:691. 5. Skinner .\1K, Fntz IB. Proc Natl Acad Sci 1985;82:114. 6. Skinner :\IK. Fetterolf P, Anthony CT. J Biol Chem 1988;263:2884. 7. Norton .I'.'-". Skinner :\rK. Endocrinology 1989; 124:2711. 8. Skinner '.\rK. Fntz 18. :\fol Cell Endocrinol 1985;40:115. 9. Skinner '.\fK. :\lcL.1chlan RI. Bremner WJ. Endocrinology 1989:63. 10. Skinner '.\TK. T.1k;.ics K. Coffey RJ. Endocrinology 1989;124:845. 11. Skinner :\!K \l"""'-'" HL. .\fol Endocrinol 1989:3:625. NEUROENDOCRINE REGULATION OF REPRODUCTION Edited by SAMUEL Ss Ca YEN University of Califomia, San Diego WYLIE VII. VALE The Salk Institute La Jolla. California • Serano Symposia, USA Norwell, Massachusetts The views expressed in this volume are the responsibility of the named authors. Great care has been taken to maintain the accuracy of the information contained in the volume. However, neither Serano Symposia, USA. Serano Laboratories, Inc., nor the editors can be held responsible for errors or any consequences arising from the use of information contained herein. Some of the names of products referred to in this book may be registered trademarks or proprietary names, although specific references to this fact may not be made; however, the use of a name without designations is not to be construed as a representation by the publisher or editors that it is in the public domain. In addition, the mention ofspecific companies or of their products or proprietary names does not imply any endorsement or recommendation on the part of the publisher or editors. Proceedings of the Symf)Osium on Neuroendocrine Regulation of Reproduction, sponsored by Sereno Symposia. USA. held November 5-9. 1989. in Napa, California I e 1990 Serono Symposia, USA 100 Longwater Circle '.'.'orwell, ~tassachusetts 02061 All rights reserved :Jo part of this book may be reproduced, stored in a retrieval system, or transmitted in anv :. r.,1 or by any means, electronic, mechanical, photocopying, microfilming, recording, or 0th er·.,:-,· without written permission from the publisher. Printed in the Crntcd States of America 

Cell-cell interactions in the testis which regulate gonadal function

https://rex.libraries.wsu.edu/view/delivery/01ALLIANCE_WSU/12406638500001842/13406638490001842

Cell-cell interactions in the testis which regulate gonadal function

Abstract

Similar works

Full text

Available Versions

Washington State University institutional repository