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).
Similar content being viewed by others
References
Skinner MK: Cell-cell interactions in the testis. Endocr Rev 12: 45-77, 1991
Dym M: Basement membrane regulation of Sertoli cells. Endocr Rev 15, 1: 102-115, 1994
Verhoeven G, Hoeben E: Les cellules péritubulaires. Med Sci 4, 11: 601-604, 1995
Templeton DG: Proteoglycans in cell regulation. Crit Rev Clin Lab Sci 29, 2: 141–184, 1992
Bertolami CN, Messadi DV: The role of proteoglycans in hard and soft tissue repair. Crit Rev Oral Biol Med 5: 311-337, 1994
Taipale J, Keski-Oja J: Growth factors in the extracellular matrix. FASEB J 11: 51-59, 1997
Nietfeld JJ: Cytokines and proteoglycans. Experiencia 49, 5: 456-468, 1993
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
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
Ackland JF, Schwartz NB, Mayo KE, Dodson RE: Nonsteroidal signals originating in the gonads. Physiol Rev 72, 3: 731-787, 1992
Leung PCK, Steele GL: Intracellular signaling in the gonads. Endocr Rev 13, 3: 476-498, 1992
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
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
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
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
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
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
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
Laurent TC, Fraser JRE: Hyaluronan. FASEB J 6: 2397-2404, 1992
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
Rapraeger A, Yeaman C: A quantitative solid-phase assay for identifying radiolabeled glycosaminoglycans in crude cell extracts. Anal Biochem 179: 361-365, 1989
Carlson DM: Structure and immunochemical properties of oligosaccharides isolated from pig submaxillary mucins. J Biol Chem 243: 616-626, 1968
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
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
Ohya T, Kaneko Y: Novel hyaluronidase from Streptomyces. Biochim Biophys Acta 198: 607-609, 1970
Prehm P: Identification and regulation of the eukaryotic hyaluronan synthase. Ciba Found Symp 143: 21-30, 1989
Carey DJ: Biological functions of proteoglycans: Use of specific inhibitors of proteoglycan synthesis. Mol Cell Biochem 104: 21-28, 1991
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
Thompson WJ: Cyclic nucleotide phosphodiesterases: Pharmacology, biochemistry and function. Pharmacol Ther 51: 13-33, 1991
Yeaman C, Rapraeger AC: Post-transcriptional regulation of syndecan-1 expression by cAMP in peritoneal macrophages. J Cell Biol 122: 941-950, 1993
Silbert JE, Sugumaran G: Intracellular membranes in the synthesis, transport, and metabolism of proteoglycans. Biochim Biophys Acta 1241: 371-384, 1995
Salmivirta M, Lidholt K, Lindahl ULF: Heparan sulfate: A piece of information. FASEB J 10: 1270-1279, 1996
Esko JD, Zhang L: Influence of core protein sequence on glycosaminoglycan assembly. Curr Opin Struct Biol 6: 663-670, 1996
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
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
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
Kleiner DE Jr, Stetler-Stevenson WG: Structural biochemistry and activation of matrix metalloproteases. Curr Opin Cell Biol 5: 891-897, 1993
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
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
Yanagishita M, Hascall VC: Cell surface heparan sulfate proteoglycans. J Biol Chem 267: 9451-9454, 1992
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
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
Sang Q-X, Dym M, Byers SW: Secreted metalloproteinases in testicular cell culture. Biol Reprod 43: 946-955, 1990
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
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
Zhang L, David G, Esko JD: Repetitive ser-gly sequences enhance heparan sulfate assembly in proteoglycans. J Biol Chem 270: 27127-27135, 1995
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
Kearns AE, Vertel BM, Schwartz NB: Topography of glycosylation and UDP-xylose production. J Biol Chem 268: 11097-11104, 1993
Abeijon C, Mandon EC, Hirchberg CB: Transporters of nucleotide sugars, nucleotide sulfate and ATP in the Golgi apparatus. TIBS 22: 203-207, 1997
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
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
Paulsson M: Basement membrane proteins: structure, assembly, and cellular interactions. Crit Rev Biochem Mol Biol 27: 93-127, 1992
David G: Integral membrane heparan sulfate proteoglycans. FASEB J 7: 1023-1030, 1993
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
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
Prehm P: Synthesis of hyaluronate in differentiated teratocarcinoma cells. Characterization of the synthase. Biochem J 211: 181-198, 1983
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
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
Toole BP: Hyaluronan and its binding proteins, the hyaladerins. Curr Opin Cell Biol 2: 839-844, 1990
Entwistle J, Hall CL, Turley EA: HA receptors: Regulators of signalling to the cytoskeleton. J Cell Biochem 61: 569-577, 1996
Author information
Authors and Affiliations
Rights 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
Issue Date:
DOI: https://doi.org/10.1023/A:1006835810773