Summary
Aqueous extracts of sheep pineals are separated on Sephadex G-25. The low molecular weight Sephadex G-25 fractions with antigonadotropic activity are ultrafiltered through the membrane UM 2. The UM 2 filtrate is subsequently filtered through the membrane UM 05. The actions of the different fractions on the anterior hypophysis and hypothalamus are discussed.
The fractions which show an activity are further separated on Sephadex G-10. The active Sephadex G-10 fractions of the UM 05 filtrate acting on the anterior hypophysisin vitro are purified by electrophoresis and paper chromatography. After elution of different fluorescence bands the main inhibitory activity is found in a region, with the same Rf value as synthetic 6-biopterin. Gas liquid chromatography and mass spectrometry studies of the isolated fractions are carried out. The mass spectrum of an isolated compound from that fraction is identical with that of synthetic 6-biopterin. Thinlayer chromatography and the results of the Crithidia fasciculata test reveal that the isolated compound is probably identical with 6-L-erythrobiopterin. The activity of the active paper chromatography fraction (C4) is compared with the activity of three synthetic biopterin-preparationsin vitro andin vivo.
The metabolic activities of biopterin derivatives and other pteridines are discussed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abelson, H. T., Spector, R., Gorka, C., Fosburg, M. Kinetics of Tetrahydrobiopterin Synthesis by Rabbit Brain Dihydrofolate Reductase. Biochem. J.171, 267–268 (1978).
Blake, C. A., Weiner, R. J., Gorski, R. A., Sawyer, C. H. Secretion of pituitary luteinizing hormone and follicle stimulating hormone in female rats made persistently oestrus and dioestrus by hypothalamus deafferentation. Endocrinology90, 855–861 (1972).
Blakley, R. I. The Biochemistry of Folic acid and Related Pteridines. Amsterdam-London: North-Holland. 1969.
Citharel, A., Ebels, L. l'Héritier, A., Moszkowska, A. Epiphyseal-hypothalamic interaction. Anin vitro study with sheep pineal fractions. Experientia29, 718–719 (1973).
Cremer-Bartels, G. Pteridines in the Mammalian Retina and Light Effects in Chemistry and Biology of Pteridines, pp. 861–870. Berlin-New York: Walter de Gruyter. 1975.
Ebels, I., Balemans, M. G. M., Verkleij, A. J. Separation of pineal extracts on Sephadex G-10. II. A spectrofluorimetric and thinlayer chromatographic study of indoles in a sheep pineal extract. J. Neuro-Visc. Rel.32, 270–282 (1972).
Ebels, I., Benson, B., Matthews, M. J. Localization of a sheep pineal antigonadotropin. Anal. Biochem.56, 546–565 (1973).
Ebels, I., Citharel, A., Moszkowska, A. Separation of pineal extracts by gelfiltration. III. Sheep pineal factors acting on the hypothalamus or on the anterior hypophysis of mice and rats inin vitro experiments. J. Neural Transm.36, 281–302 (1975).
Ebels, L. Moszkowska, A., Scémama, A. Étudein vitro des extracts épiphysaires fractionnés. Résultats préliminaires. C.R. Acad. Sci.260, 5126–5129 (1965).
Halpern, R., Holpern, B. C., Stea, B., Dunlap, A., Conklin, K., Clark, B., Ashe, H., Sperling, L., Halpern, J. A., Hardy, D., Smith, R. A. Pterin-6-aldehyde, a cancer cell catabolite: Identification and application in diagnosis and treatment of human cancer. Proc. Natl. Acad. Sci. U.S.A.74, 587–591 (1977).
Hori, S., Ohtani, S. An activating substance for tryptophan-5-monooxygenase in extracts of bovine pineal glands. Fed. Proc.37, 1629 (1978).
Hosoda, S., Glick, D. Studies in Histochemistry LXXIX. Properties of tryptophan hydroxylase from neoplastic murine mast cell. J. Biol. Chem.241, 192–196 (1966).
Hus-Citharel, A., Roseau, S., Zurburg, W. Effects of precocious pineal-ectomy and hemicastration on pituitary and plasma LH levels in immature male rats. J. Neural Transm.40, 33–46 (1977).
Kalckar, H. M., Klenow, H. Milk Xanthopterin oxidase and pteroyl-glutamic acid. J. Biol. Chem.172, 349–350 (1948).
Kalckar, H. M., Kjeldgaard, N. O., Klenow, H. Inhibition of xanthine oxidase and related enzymes by 6-pteridyl aldehyde. J. Biol. Chem.174, 771–772 (1948).
Kalckar, H. M., Kjeldgaard, N. O., Klenow, H. 2-amino-4-hydroxy-6-formylpteridine, an inhibitor of purine and pteridine oxidases. Biochim. Biophys. Acta5, 586–594 (1950).
Kokolis, N., Mylonas, N., Ziegler, I. Pteridine and Riboflavin in Tumor Tissue and the Effect of Chloramphenicol and Isoxanthopterin. Zeitschr. f. Naturforschung27 b, 292–295 (1972).
Leeming, R. J., Blair, J. A., Green, A., Raine, D. N. Biopterin derivatives in normal and phenyl-Ketonuric patients after oral loads of L-phenylalanine, L-tyrosine and L-tryptophan. Arch. of Disease in Childhood51, 771–777 (1976).
l'Hélias, C. Contrôle chez les Insectes de la synthèse des hormones de croissance par les ptérines agissant par induction ou par répression on fonction de la température et de la photopériode. Ann. d'Endocrinologie25 (suppl.), 66–71 (1964).
l'Hélias, C. Altérations possibles dans la transmission des informations génétiques chez la Drosophile par injections d'extraits de chrysalides diapausante (Pieris brassicae), traitées par des ptérines. Ann. d'Endocrinologie31, 578–581 (1970).
l'Hélias, C. Hormone juvénile de Pieris brassicae diapausante et mutations. Ann. d'Endocrinologie (Paris)35, 63–85 (1975).
Lloyd, T., Markey, S., Weiner, N. Identification of 2-amino-4-hydroxy substituted pteridines by gas liquid chromatography and mass spectrometry. Anal. Biochem.42, 108–112 (1971).
Lloyd, T., Weiner, N. Isolation and characterization of a tyrosine hydroxylase co-factor from bovine adrenal medulla. Molecular Pharmacology7, 569–580 (1971).
Lowry, O. H., Bessey, O. A., Crawford, E. J. Photolytic and enzymatic transformations of pteroylglutamic acid. J. Biol. Chem.180, 389–398 (1949).
Moszkowska, A. Étudein vitro du rôle de l'épiphyse dans l'excrétion d'hormones gonadotropes hypophysaires. C.R. Acad. Sci.247, 1659–1662 (1958).
Moszkowska, A. Contribution à l'étude du mécanisme de l'antagonisme épiphyso-hypophysaire. Progr. Brain Research10, 564–576 (1965).
Moszkowska, A., Citharel, A., l'Héritier, A., Ebels, I., Laplante, E. Some new aspects of a sheep pineal gonadotropic inhibiting activity inin vitro experiments. Experientia30, 964–965 (1974).
Moszkowska, A., Ebels, I. A study of the antigonadotropic action of synthetic arginine vasotocin. Experientia24, 610–611 (1968).
Moszkowska, A., Ebels, I. A study of the pineal body on the gonadotropic function of the hypophysis. J. Neuro-Visc. Rel., Suppl. X, pp. 160–176. Wien-New York: Springer. 1971.
Moszkowska, A., Heersche, J. N. M.: Action inhibitrice de l'épiphyse sur l'excrétion gonadotrope hypophysaire. Excerpta Medica, Intern. Congress Series48, XXII. International Congress of Physiological Sciences, Leiden, September 10–17, N0518 (1962).
Moszkowska, A., Hus-Citharel, A., l'Héritier, A., Zurburg, W., Ebels, I. Separation of pineal extracts by gelfiltration. V. Location by paper chromatography of a sheep pineal principle inhibiting hypophyseal gonadotropic activity. J. Neural Transm.38, 239–247 (1976).
Moszkowska, A., Scémama, A., Lombard, M. M., Héry, M. Experimental modulation of hypothalamic content of the gonadotropic releasing factors by pineal factors in the rat. J. Neural Transm.34, 11–22 (1973).
Norris, E. R., Majnarich, J. J. Effect of Xanthopterin on cell proliferation in bone marrow cultures. Amer. J. Physiol.152, 175–178 (1948).
Norris, E. R., Majnarich, J. J. Further studies on Xanthopterin and other pteridines in bone marrow cultures. Amer. J. Physiol.152, 652–657 (1948).
Norris, E. R., Majnarich, J. J. Xanthopterin in rat anemia produced by sulfathiazole. Amer. J. Physiol.152, 179–182 (1948).
Norris, E. R., Majnarich, J. J. Effect of Xanthopterin and other pteridines on the rate of cell proliferation in tissue cell cultures. Amer. J. Physiol.153, 488–491 (1948).
Norris, E. R., Majnarich, J. J. Effect of pteridines and blood serum on neoplastic cell culturein vitro. Amer. J. Physiol.153, 492–495 (1948).
Norris, E. R., Majnarich, J. J. Effect of pteridines and blood sera on human bone marrow cellsin vitro. Amer. J. Physiol.153, 496–498 (1948).
Petering, H. G., Schmitt, J. A. Studies in Enzyme inhibition. I. Action of some simple pteridines on Xanthine oxidase. J. Amer. Chem. Soc.72, 2995–2998 (1950).
Pfleiderer, W. Chemistry and biology of pteridines. Berlin-New York: Walter de Gruyter. 1975.
Rembold, H., Gyure, W. L. Biochemie der Pteridine. Angewandte Chemie84, 1088–1099 (1972).
Van der Have-Kirchberg, M. M. L., De Morée, A., Van Laar, J. F., Gerwig, G. J., Versluis, C., Ebels, I., Hus-Citharel, A., l'Héritier, A., Roseau, S., Zurburg, W., Moszkowska, A. Separation of pineal extracts by gelfiltration. VI. Isolation and identification from sheep pineals of biopterin; comparison of the isolated compound with some synthetic pteridines and the biological activity inin vitro andin vivo bioassays. J. Neural Transm.40, 205–220 (1977).
Visconti, M., Bieri, J. Über Pterinchemie. Neue Synthesen von Folsäureanalogen. Helv. Chim. Acta54, 2291–2297 (1971).
Zurburg, W., Ebels, I. Separation of pineal extracts by gelfiltration. I. Isolation from sheep pineals of a substance with special fluorescence characteristics. J. Neural Transm.35, 117–124 (1974).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ebels, I., de Morée, A., Hus-Citharel, A. et al. A survey of some active sheep pineal fractions and a discussion on the possible significance of pteridines in those fractions inin vitro andin vivo assays. J. Neural Transmission 44, 97–116 (1979). https://doi.org/10.1007/BF01252705
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01252705