Skip to main content
Log in

Regulation of proteoglycan and hyaluronan synthesis by elevated level of intracellular cyclic adenosine monophosphate in peritubular cells from immature rat testis

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The effects of an increase in intracellular cAMP concentration on proteoglycan (PG) synthesis by peritubular (PT) cells from immature rat testis were investigated. In the presence of dBcAMP for 72 h, the [3H]-hexosamine incorporation in secreted PG and in cellassociated PG was reduced, whereas [35S]-sulfate radioactivity was enhanced in secreted PG and not affected in cell-associated PG. Cholera toxin and IBMX, known to generate high intracellular cAMP levels, induced similar changes. Cyclic AMP did not alter PG protein moiety synthesis but enhanced PG turnover. Cholera toxin and dBcAMP profoundly modified PG characteristics: (1) Apparent molecular weight of PG was increased. (2) This was due to an increase in glycosaminoglycans (heparan sulfate (HS) and chondroitin sulfate (CS)) length. (3) The number of glycosaminoglycan chains was presumably reduced. (4) Heparan sulfate and chondroitin sulfate chains of medium and cell layer-associated PG appeared oversulfated. (5) The pattern of cell layer associated PG was modified with a decrease in HSPG and a correlative increase in CSPG. Cholera toxin and dBcAMP also dramatically stimulated hyaluronan synthesis by possible phosphorylation induced activation of hyaluronan synthase(s).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Skinner MK: Cell-cell interactions in the testis. Endocr Rev 12: 45-77, 1991

    Google Scholar 

  2. Dym M: Basement membrane regulation of Sertoli cells. Endocr Rev 15, 1: 102-115, 1994

    Google Scholar 

  3. Verhoeven G, Hoeben E: Les cellules péritubulaires. Med Sci 4, 11: 601-604, 1995

    Google Scholar 

  4. Templeton DG: Proteoglycans in cell regulation. Crit Rev Clin Lab Sci 29, 2: 141–184, 1992

    Google Scholar 

  5. Bertolami CN, Messadi DV: The role of proteoglycans in hard and soft tissue repair. Crit Rev Oral Biol Med 5: 311-337, 1994

    Google Scholar 

  6. Taipale J, Keski-Oja J: Growth factors in the extracellular matrix. FASEB J 11: 51-59, 1997

    Google Scholar 

  7. Nietfeld JJ: Cytokines and proteoglycans. Experiencia 49, 5: 456-468, 1993

    Google Scholar 

  8. Cailleau J, Vermeire S, Verhoeven G: Independent control of the production of insulin-like growth factor I and its binding protein by culture testicular cells. Mol Cell Endocrinol 69: 79-89, 1990

    Google Scholar 

  9. Thiébot B, Bichoualne L, Langris M, Bonnamy PJ, Barbey P, Carreau S, Bocquet J: IGF-1 stimulates synthesis of undersulfated proteoglycans and of hyaluronic acid by peritubular cells from immature rat testis. Biochim Biophys Acta 1358: 127-141, 1997

    Google Scholar 

  10. Ackland JF, Schwartz NB, Mayo KE, Dodson RE: Nonsteroidal signals originating in the gonads. Physiol Rev 72, 3: 731-787, 1992

    Google Scholar 

  11. Leung PCK, Steele GL: Intracellular signaling in the gonads. Endocr Rev 13, 3: 476-498, 1992

    Google Scholar 

  12. Myake MD, Yamamoto M, Narita H, Hashimoto J, Mitsuya H: Evidence for contractility of the human seminiferous tubule confirmed by its response to noradrenaline and acetylcholine. Fert Ster 46: 734-737, 1986

    Google Scholar 

  13. Ailenberg M, Tung PS, Fritz IB: Transforming growth factor-β elicits shape changes and increases contractility of testicular peritubular cells. Biol Reprod 42: 499-509, 1990

    Google Scholar 

  14. Howl J, Rudge SA, Lavis RA, Davies AR, Parslow RA, Hughes PJ, Kirk CJ, Michell RH, Wheatley M: Rat testicular myoid cells express vasopressin receptors: Receptor structure, signal transduction and developmental regulation. Endocrinology 136, 5: 2206-2212, 1995

    Google Scholar 

  15. Paulssen RH, Paulssen EJ, Gordeladze JO, Hansson V, Haugen TB: Cell-specific expression of guanine nucleotide-binding proteins in rat testicular cells. Biol Reprod 45: 566-571, 1991

    Google Scholar 

  16. Tung PS, Fritz IB: Morphogenetic restructuring and formation of basement membranes by Sertoli cells and testis peritubular cells in co-culture: Inhibition of the morphogenetic cascade by cyclic AMP derivatives and by blocking direct cell contact. Dev Biol 120: 139-153, 1987

    Google Scholar 

  17. Tomida M, Koyama H, Ono T: Effects of adenosine 3′, 5′-cyclic monophosphate and serum on synthesis of hyaluronic acid in confluent rat fibroblasts. Biochem J 162: 539-543, 1977

    Google Scholar 

  18. Bichoualne L, Thiébot B, Langris M, Barbey P, Houlhaj H, Bocquet J: Membrane associated proteoglycans in rat testicular peritubular cells. Mol Cell Biochem 140: 37-48, 1994

    Google Scholar 

  19. Laurent TC, Fraser JRE: Hyaluronan. FASEB J 6: 2397-2404, 1992

    Google Scholar 

  20. West DC, Sattar A, Kumar S: A simplified in situ solubilisation procedure for determination of DNA and cell number in tissue cultured mammalian cells. Anal Biochem 147: 289-295, 1985

    Google Scholar 

  21. Rapraeger A, Yeaman C: A quantitative solid-phase assay for identifying radiolabeled glycosaminoglycans in crude cell extracts. Anal Biochem 179: 361-365, 1989

    Google Scholar 

  22. Carlson DM: Structure and immunochemical properties of oligosaccharides isolated from pig submaxillary mucins. J Biol Chem 243: 616-626, 1968

    Google Scholar 

  23. Conrad GW, Hamilton C, Haynes E: Differences in glycosaminoglycans synthesized by fibroblast-like cells from chick cornea, heart and skin. J Biol Chem 252: 6861-6870, 1977

    Google Scholar 

  24. Kleine TO, Merten B: A procedure for the simultaneous determination of small quantities of hyaluronate and isomeric chondroitin sulfate by chondroitinases. Anal Biochem 118: 185-90, 1981

    Google Scholar 

  25. Ohya T, Kaneko Y: Novel hyaluronidase from Streptomyces. Biochim Biophys Acta 198: 607-609, 1970

    Google Scholar 

  26. Prehm P: Identification and regulation of the eukaryotic hyaluronan synthase. Ciba Found Symp 143: 21-30, 1989

    Google Scholar 

  27. Carey DJ: Biological functions of proteoglycans: Use of specific inhibitors of proteoglycan synthesis. Mol Cell Biochem 104: 21-28, 1991

    Google Scholar 

  28. Klinz FJ, Costa T: Cholera toxin ADP-ribosylates the receptor-coupled form of pertussis toxin-sensitive G-proteins. Biochem Biophys Res Commun 165: 554-560, 1989

    Google Scholar 

  29. Thompson WJ: Cyclic nucleotide phosphodiesterases: Pharmacology, biochemistry and function. Pharmacol Ther 51: 13-33, 1991

    Google Scholar 

  30. Yeaman C, Rapraeger AC: Post-transcriptional regulation of syndecan-1 expression by cAMP in peritoneal macrophages. J Cell Biol 122: 941-950, 1993

    Google Scholar 

  31. Silbert JE, Sugumaran G: Intracellular membranes in the synthesis, transport, and metabolism of proteoglycans. Biochim Biophys Acta 1241: 371-384, 1995

    Google Scholar 

  32. Salmivirta M, Lidholt K, Lindahl ULF: Heparan sulfate: A piece of information. FASEB J 10: 1270-1279, 1996

    Google Scholar 

  33. Esko JD, Zhang L: Influence of core protein sequence on glycosaminoglycan assembly. Curr Opin Struct Biol 6: 663-670, 1996

    Google Scholar 

  34. Rapraeger A: Transforming growth factor (type beta) promotes the addition of chondroitin sulfate chains to the cell surface proteoglycan (syndecan) of mouse mammary epithelia. J Cell Biol 109: 2509-2518, 1989

    Google Scholar 

  35. Kitagawa H, Tsutsumi K, Ujikawa M, Goto F, Tamura J, Neumann KW, Ogawa T, Sugahara K: Regulation of chondroitin sulfate biosynthesis by specific sulfatation-acceptor specificity of serum beta-GalNac transferase revealed by structurally defined oligosaccharides. Glycobiology 7: 531-537, 1997

    Google Scholar 

  36. Hascall VC, Heinegard DK, Wight TN: Proteoglycans, metabolism and pathology. In: E.D. Hay (ed). Cell Biology of Extracellular Matrix. Plenum press, NY, 1991, pp 149-175

    Google Scholar 

  37. Kleiner DE Jr, Stetler-Stevenson WG: Structural biochemistry and activation of matrix metalloproteases. Curr Opin Cell Biol 5: 891-897, 1993

    Google Scholar 

  38. Subramanian SV, Fitzgerald ML, Bernfield M: Regulated shedding of syndecan-1 and 4 ectodomains by thrombin and growth factor receptor activation. J Biol Chem 272: 14713-14720, 1997

    Google Scholar 

  39. Ishihara M, Fedarko NS, Conrad HE: Involvement of phosphatidylinositol and insulin in the coordinate regulation of proteoheparan sulfate metabolism and hepatocyte growth. J Biol Chem 262: 4708-4716, 1987

    Google Scholar 

  40. Yanagishita M, Hascall VC: Cell surface heparan sulfate proteoglycans. J Biol Chem 267: 9451-9454, 1992

    Google Scholar 

  41. Hoeben E, Van Aelst I, Swinnen JV, Opdenakker G, Verhoeven G: Gelatinase A secretion and its control in peritubular and Sertoli cell cultures: Effects of hormones, second messengers and inducers of cytokine production. Mol Cell Endocrinol 118: 37-46, 1996

    Google Scholar 

  42. Ailenberg M, Stetler-Stevenson WG, Fritz IB: Secretion of latent type IV procollagenase and active type IV collagenase by testicular cells in culture. Biochem J 279: 75-80, 1991

    Google Scholar 

  43. Sang Q-X, Dym M, Byers SW: Secreted metalloproteinases in testicular cell culture. Biol Reprod 43: 946-955, 1990

    Google Scholar 

  44. Sang Q-X, Stetler-Stevenson WG, Liotta LA, Byers SW: Identification of type IV collagenase in rat testicular cell culture: Influence of peritubular-Sertoli cell interactions. Biol Reprod 43: 956-964, 1990

    Google Scholar 

  45. Imai Y, Ibaraki K, Odajima R, Shishiba Y: Effects of dibutyryl cyclic AMP on hyaluronan and proteoglycan synthesis by retroocular tissue fibroblasts in culture. Endocr J 6: 645-654, 1994

    Google Scholar 

  46. Zhang L, David G, Esko JD: Repetitive ser-gly sequences enhance heparan sulfate assembly in proteoglycans. J Biol Chem 270: 27127-27135, 1995

    Google Scholar 

  47. Toma L, Pinbal MAS, Dietrich CP, Nader HB, Hirschberg CB: Transport of UDP-galactose into the Golgi lumen regulates the biosynthesis of proteoglycans. J Biol Chem 271: 3897-3901, 1996

    Google Scholar 

  48. Kearns AE, Vertel BM, Schwartz NB: Topography of glycosylation and UDP-xylose production. J Biol Chem 268: 11097-11104, 1993

    Google Scholar 

  49. Abeijon C, Mandon EC, Hirchberg CB: Transporters of nucleotide sugars, nucleotide sulfate and ATP in the Golgi apparatus. TIBS 22: 203-207, 1997

    Google Scholar 

  50. Beck L, Mularoni A, Cardis P, Adessi GL, Nicollier M: Adenosine 3′, 5′-monophosphate mediates progesterone effect on sulfate uptake in endometrial epithelial cells. Endocrinology 136: 1737-1743, 1995

    Google Scholar 

  51. Klaassen CD, Boles JW: Sulfation and sulfotransferases 5. The importance of 3′-phosphoadenosine 5'-phosphosulfate (PAPS) in the regulation of sulfation. FASEB J 11: 404-418, 1997

    Google Scholar 

  52. Paulsson M: Basement membrane proteins: structure, assembly, and cellular interactions. Crit Rev Biochem Mol Biol 27: 93-127, 1992

    Google Scholar 

  53. David G: Integral membrane heparan sulfate proteoglycans. FASEB J 7: 1023-1030, 1993

    Google Scholar 

  54. Roskelley CD, Srebrow A, Bissel MJ: A hierarchy of ECM-mediated signalling regulates tissue-specific gene expression. Curr Opin Cell Biol 7: 736-747, 1995

    Google Scholar 

  55. Ko CW, Bhandari B, Yee J, Terhune WC, Maldonado R, Kasinath BS: Cyclic AMP regulates basement membrane heparan sulfate proteoglycan, perlecan, metabolism in rat glomerular epithelial cells. Mol Cell Biochem 162: 65-73, 1997

    Google Scholar 

  56. Prehm P: Synthesis of hyaluronate in differentiated teratocarcinoma cells. Characterization of the synthase. Biochem J 211: 181-198, 1983

    Google Scholar 

  57. Spicer AP, Olson JS, McDonald JA: Molecular cloning and characterization of a cDNA encoding the third putative mammalian hyaluronan synthase. J Biol Chem 272: 8957-8961, 1997

    Google Scholar 

  58. Klewes L, Prehm P: Intracellular signal transduction for serum activation of the hyaluronan synthase in eukariotic cell lines. J Cell Physiol 160: 539-544, 1994

    Google Scholar 

  59. Toole BP: Hyaluronan and its binding proteins, the hyaladerins. Curr Opin Cell Biol 2: 839-844, 1990

    Google Scholar 

  60. Entwistle J, Hall CL, Turley EA: HA receptors: Regulators of signalling to the cytoskeleton. J Cell Biochem 61: 569-577, 1996

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Thiébot, B., Langris, M., Bonnamy, PJ. et al. Regulation of proteoglycan and hyaluronan synthesis by elevated level of intracellular cyclic adenosine monophosphate in peritubular cells from immature rat testis. Mol Cell Biochem 187, 99–112 (1998). https://doi.org/10.1023/A:1006835810773

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1006835810773

Navigation