The Testis pp 30-42 | Cite as

MIS Actions in the Developing Testis

  • Mary Min-chin Lee
Conference paper
Part of the Serono Symposia USA book series (SERONOSYMP)

Abstract

Müllerian inhibiting substance (MIS), a gonadal glycoprotein in the TGF-β family of growth and differentiation factors, is recognized primarily for its role in promoting involution of the Müllerian ducts during normal male sexual differentiation. Continued synthesis of MIS by Sertoli cells and expression of its cognate type II receptor in the postnatal testis, however, raised the possibility of additional functions for MIS. We hypothesized that MIS plays an important role in the regulation of Leydig-cell proliferation and maturation during postnatal testicular development. This chapter will summarize the expression and binding characteristics of the MIS receptor in the postnatal testis and elucidate the actions of MIS in Leydig cells at different stages of maturation using a primary rat Leydig-cell culture model. These data suggest that this fetal growth inhibitor affects androgen production by downregulating steroidogenic enzymes and helps to maintain a normal complement of Leydig cells by constraining their proliferation, thus supporting a direct role for MIS in the developing testis.

Keywords

Sertoli Cell Leydig Cell Thymidine Incorporation Steroidogenic Enzyme Mullerian Duct 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. 1.
    Jost A. Recherches sur la differentiation sexuelle de l’embryon de lapin. Arch Anat Microsc Morphol Exp 1947; 36: 271–315.Google Scholar
  2. 2.
    Donahoe PK, Cate RL, MacLaughlin DT, Epstein J, Fuller AF, Takahashi M, et al. Mullerian inhibiting substance: gene structure and mechanism of action of a fetal regressor. Rec Prog Horm Res 1987;43:431–67.PubMedGoogle Scholar
  3. 3.
    Josso N, Picard JY. Anti-Mullerian hormone. Physiol Rev 1986;66(4): 1038–90.Google Scholar
  4. 4.
    Cate RL, Mattaliano RJ, Hession C, Tizard R, Farber NM, Cheung A, et al. Isolation of the bovine and human genes for Mullerian inhibiting substance and expres¬sion of the human gene in animal cells. Cell 1986;45(5):685–98.CrossRefGoogle Scholar
  5. 5.
    Picard JY, Benarous R, Guerrier D, Josso N, Kahn A. Cloning and expression of cDNA for anti-Mullerian hormone. Proc Natl Acad Sci USA 1986;83(15): 5464–68.CrossRefGoogle Scholar
  6. 6.
    MacLaughlin DT, Hudson PL, Graciano AL, Kenneally MK, Ragin RC, Manganaro TF, et al. Mullerian duct regression and anti-proliferative bioactivities of Mullerian inhibiting substance reside in its carboxy-terminal domain. Endocrinology 1992; 131(1):291–96.CrossRefGoogle Scholar
  7. 7.
    Teixeira J, He WW, Shah PC, Morikawa N, Lee MM, Catlin EA, et al. Developmental expression of a candidate Mullerian inhibiting substance type II receptor. Endocrinology 1996; 137(1): 160–65.CrossRefGoogle Scholar
  8. 8.
    di Clemente N, Wilson C, Faure E, Boussin L, Carmillo P, Tizard R, et al. Cloning, expression, and alternative splicing of the receptor for anti–Mullerian hormone. Mol Endocrinol 1994;8(8): 1006–20.CrossRefGoogle Scholar
  9. 9.
    Baarends WM, van Helmond MJ, Post M, van der Schoot P, Hoogerbrugge JW, de Winter J, et al. A novel member of the transmembrane serine/threonine kinase receptor family is specifically expressed in the gonads and in mesenchymal cells adjacent to the mullerian duct. Development 1994; 120(1): 189–97.Google Scholar
  10. 10.
    Massague J . Receptors for the TGF-β family. Cell 1992;69:1067–70.PubMedCrossRefGoogle Scholar
  11. 11.
    Kuroda T, Lee MM, Haqq CM, Powell DM, Manganaro TF, Donahoe PK. Mullerian inhibiting substance ontogeny and its modulation by follicle-stimulating hormone in the rat testes. Endocrinology 1990; 127(4): 1825–32.CrossRefGoogle Scholar
  12. 12.
    Lee MM, Cate RL, Donahoe PK, Waneck GL. Developmentally regulated polyadenylation of two discrete messenger ribonucleic acids for Mullerian inhibiting substance. Endocrinology 1992;130(2):847–53.CrossRefGoogle Scholar
  13. 13.
    Baarends WM, Hoogerbrugge JW, Post M, Visser JA, De Rooij D, Parvinen M, et al. Anti-Mullerian hormone and anti-Mullerian hormone type II receptor messenger ribonucleic acid expression during postnatal testis development and in the adult testis of the rat. Endocrinology 1995;136(12):5614–22.PubMedCrossRefGoogle Scholar
  14. 14.
    Lyet L, Louis F, Forest MG, Josso N, Behringer RR, Vigier B. Ontogeny of reproductive abnormalities induced by deregulation of anti-mullerian hormone expression in transgenic mice. Biol Reprod 1995;52(2):444–54.CrossRefGoogle Scholar
  15. 15.
    Behringer RR, Cate RL, Froelick GJ, Palmiter RD, Brinster RL. Abnormal sexual development in transgenic mice chronically expressing mullerian inhibiting substance. Nature 1990;345(6271): 167–70.CrossRefGoogle Scholar
  16. 16.
    Racine C, Rey R, Forest M, Louis F, Ferre A, Huhtaniemi I, et al. Receptors for anti-Mullerian hormone on Leydig cells are responsible for its effects on steroidogenesis and cell differentiation. Proc Natl Acad Sci USA 1998;95:594–99.PubMedCrossRefGoogle Scholar
  17. 17.
    Mishina Y, Rey R, Finegold MJ, Matzuk MM, Josso N, Cate RL, et al. Genetic analysis of the Mullerian-inhibiting substance signal transduction pathway in mammalian sexual differentiation. Genes Dev 1996;10:2577–87.PubMedCrossRefGoogle Scholar
  18. 18.
    Behringer RR, Finegold MJ, Cate RL. Mullerian inhibiting substance function during mammalian sexual development. Cell 1994;79(3):415–25.CrossRefGoogle Scholar
  19. 19.
    Lee MM, Seah CC, Masiakos PT, Sottas CM, Preffer FI, Donahoe PK, et al. Mullerian inhibiting substance type II receptor expression and function in purified rat Leydig cells. Endocrinology 1999;140:2819–27.PubMedCrossRefGoogle Scholar
  20. 20.
    Klinefelter GR, Kelce WR, Hardy MP. Isolation and culture of Leydig cells from adult rats. Meth Toxicol 1993;3:166–81.Google Scholar
  21. 21.
    Ge RS, Shan LX, Hardy MP. Pubertal development of Leydig cells. In: Payne AH, Hardy MP, Russell LD, eds. The Leydig cell. Vienna, VA: Cache River Press, 1996: 159–74.Google Scholar
  22. 22.
    Benton L, Shan LX, Hardy MP. Differentiation of adult Leydig cells. J Steroid Biochem Mol Biol 1995;53(l-6):61–68.CrossRefGoogle Scholar
  23. 23.
    Mather J, Phillips DM. Primary culture of testicular somatic cells. In: Methods for serum-free culture of cells of the endocrine system. New York: Alan R. Liss, 1984:29–45.Google Scholar
  24. 24.
    Payne AH, Downing JR, Wong KL. Luteinizing hormone receptors and testosterone synthesis in two distinct populations of Leydig cells. Endocrinology 1980;106:1424–29.PubMedCrossRefGoogle Scholar
  25. 25.
    MacLaughlin DT, Epstein J, Donahoe PK. Bioassay, purification, cloning, and expression of Mullerian inhibiting substance. Meth Enzymol 1991;198:358–69.PubMedCrossRefGoogle Scholar
  26. 26.
    Hudson PL, Dougas I, Donahoe PK, Cate RL, Epstein J, Pepinsky RB, et al. An immunoassay to detect human Mullerian inhibiting substance in males and females during normal development. J Clin Endocrinol Metab 1990;70(1): 16–22.CrossRefGoogle Scholar
  27. 27.
    Picon R . Action du testicule foetal sur le developpement in vitro des canaux de Muller chez le rat. Arch Anat Microsc Morphol Exp 1969;58(1):1–19.PubMedGoogle Scholar
  28. 28.
    Donahoe PK, Ito Y, Hendren WH. A graded organ culture assay for the detection of Mullerian inhibiting substance. J Surg Res 1977;23(2): 141–48.CrossRefGoogle Scholar
  29. 29.
    Cochran R, Ewing L, Niswender G. Serum levels of follicle stimulating hormone, luteinizing hormone, prolactin, testosterone, 5α-dihydrotestosterone, 5α-androstane-3α, 17β-diol, 5α-androstane-3β-, 17β-diol, and 17β-estradiol from male beagles with spontaneous or induced benign prostatic hyperplasia. Invest Urol. 1981;19:142–47.PubMedGoogle Scholar
  30. 30.
    Shan LX, Phillips DM, Bardin CW, Hardy MP. Differential regulation of steroidogenic enzymes during differentiation optimizes testosterone production by adult rat Leydig cells. Endocrinology. 1993;133(5):2277–83.CrossRefGoogle Scholar
  31. 31.
    Ackland JF, Schwartz NB, Mayo KE, Dodson RE. Nonsteroidal signals originating in the gonads. Physiol Rev 1992;72:731–87.PubMedGoogle Scholar
  32. 32.
    Skinner MK . Cell-cell interactions in the testis. Endocrine Rev 1991;12:45–77.CrossRefGoogle Scholar
  33. 33.
    Vergouwen R, Jacobs S, Huiskamp R, Davids J, de Rooj D. Proliferative activity of gonocytes, Sertoli cells and interstitial cells during testicular development in mice. J Reprod Fertil 1991;93:233–43.PubMedCrossRefGoogle Scholar
  34. 34.
    Hardy MP, Gelber SJ, Zhou ZF, Penning TM, Ricigliano JW, Ganjam VK, et al. Hormonal control of Leydig cell differentiation. Ann NY Acad Sci 1991 ;637(152): 152–63.CrossRefGoogle Scholar
  35. 35.
    Ewing LL, Keeney DS. Leydig cells: structure and function. In: Desjardins C, Ewing LL, eds. Cell and molecular biology of the testis. New York: Oxford University Press, 1993:137–65.Google Scholar
  36. 36.
    Payne AH, Youngblood GL. Regulation of expression of steroidogenic enzymes in Leydig cells: Biol Reprod 1995;52:217–25.PubMedCrossRefGoogle Scholar
  37. 37.
    Shan L, Hardy DO, Catterall JF, Hardy MP. Effects of luteinizing hormone (LH) and androgen on steady state levels of messenger ribonucleic acid for LH receptors, androgen receptors, and steroidogenic enzymes in rat Leydig cell progenitors in vivo. Endocrinology 1995; 136(4): 1686–93.CrossRefGoogle Scholar
  38. 38.
    Joseph D, Hall S, French F. Rat androgen-binding protein: evidence for identical subunits and amino acid sequence homology with human sex hormone-binding globulin. Proc Natl Acad Sci USA 1987;84:339–43.PubMedCrossRefGoogle Scholar
  39. 39.
    Ercolani L, Florence B, Denaro M, Alexander-Bridges M. Isolation and complete sequence of a functional human glyceraldehyde-3-phosphate dehydrogenase gene. J Biol Chem 1988;263:15335–41.PubMedGoogle Scholar
  40. 40.
    Shan L, Hardy M. Developmental changes in levels of luteinizing hormone receptor and androgen receptor in rat Leydig cells. Endocrinology 1992; 131(3): 1107–14.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York, Inc. 2000

Authors and Affiliations

  • Mary Min-chin Lee

There are no affiliations available

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