Peptidic and Proteic Substances Isolated from Pineals and Their Relation to the Hypophysial-Hypothalamic-Gonadal Axis

  • I. Ebels
Part of the NATO Advanced Science Institutes Series book series (NSSA, volume 65)


At the ultrastructural level, processes implicated in the synthesis and release of peptidic/proteic compounds have been clearly identified in pineal specific cells (Collin, 1979, 1981; Collin and Oksche, 1981; Pévet, 1979, 1981a,b, 1982a,b). Thus the synthesis and release of peptidic/proteic substances cannot be discarded. The isolation, purification and characterization of this class of pineal compounds have however presented a formidable challenge, since extraction methods for peptide purification have failed to yield large quantities of pure compounds, sufficient for structure elucidation. Moreover, a simple and specific bioassay, indispensable for the isolation of biologically active compounds has not been available till now. Different observations however support the presence of pineal peptidic and proteic substances showing a definite biological activity.


Luteinizing Hormone Pineal Gland Pineal Organ Pineal Body Tropic Activity 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ariëns Kappers, J., Smith, A.R., and de Vries, R.A.C., 1974, The mammalian pineal gland and its control of hypothalamic activity, Progr. Brain Res. 41:149.Google Scholar
  2. Balemans, M.G.M., Ebels, I., and Vonk-Visser, D.M.A., 1970, Separation of pineal extracts on Sephadex G-10. I. A spectrofluori-metric study of indoles in a cockerel pineal extract., J. Neurovisc. Relat. 32: 65.PubMedCrossRefGoogle Scholar
  3. Bartke, A., Croft, B.T., and Dalterio, S., 1975, Prolactin restores plasma testosterone levels and stimulates testicular growth in hamsters exposed to short daylength, Endocrinology 97: 1601.Google Scholar
  4. Bensinger, R., Vaughan, M.K., and Klein, D.C., 1973, Isolation of a non-melatonin lipophilic antigonadotrophic factor from the bovine pineal gland. Fed. Proc.Fed. Am. Socs. Exp. Biol. 32:225.Google Scholar
  5. Benson, B., and Ebels, I., 1981, Other pineal peptides and related substances physiological implications for reproductive biology, in: “The Pineal Gland,” Vol. II, Reproductive Effects, R.J. Reiter ed., CRC Press, Inc. Boca Raton, Florida.Google Scholar
  6. Benson, B., Larsen, B.R., Findell, P,R., and Orstead, K.M., 1982, Participation of pineal peptides in reproduction, in press.Google Scholar
  7. Benson, B., and Matthews, M.J., 1980, Possible role of prolactin and pineal prolactin-regulating substances in pineal-mediated gonadal atrophy in hamsters, Hormone Res., 12: 137.PubMedCrossRefGoogle Scholar
  8. Benson, B., and Orts, R.J., 1972, Regulation of ovarian growth by the pineal, in: “Regulation of Organ and Tissue Growth,” Academic Press, New York.Google Scholar
  9. Benson, B., Matthews, M.J., Hadley, M.E., Powers, S., and Hruby, V.J., 1976a, Differential localization of antigonadotropic and vasotocic activities in bovine and rat pineal, Life Sci. 19: 747.PubMedCrossRefGoogle Scholar
  10. Benson, B., Matthews, M.J.,and Hruby, V.J., 1976b, Characterization and effects of a bovine pineal antigonadotropic peptide, Am. Zool. 16: 17.Google Scholar
  11. Bex, F.,Bartke, A., Goldman, D.B., and Dalterio, S., 1978, Prolactin, growth hormone,luteinizing hormone receptors, and seasonal changes in testicular activity in the golden hamster, Endocrinology 103: 2069.PubMedCrossRefGoogle Scholar
  12. Blask, D.E., Vaughan, M.K., Reiter, R.J., Johnson, L.Y., and Vaughan, G.M., 1976, Prolactin-releasing and release-inhibiting factor activities in the bovine, rat and human pineal gland. In vitro and in vivo studies, Endocrinology 99: 152.Google Scholar
  13. Chang, N., Ebels, I., and Benson, B., 1979, Preliminary characterization of bovine pineal prolactin releasing (PPRF) and release-inhibiting factor (PPIF) activity, J. Neural Transm. 46: 139.PubMedCrossRefGoogle Scholar
  14. Cheesman, D.W., 1970, Structural elucidation of a gonadotropininhibiting substance from the bovine pineal gland, Biochim. Biophys, Acta. 207:247.Google Scholar
  15. Cheesman, D.W., and Fariss, B.L., 1970, Isolation and characterization of a gonadotropin-inhibiting substance from the bovine pineal gland, Proc. Soc. Exp. Biol. Med., 133:1254.Google Scholar
  16. Citharel, A., Ebels, I., L’Héritier, A., and Moszkowska, A., 1973, Epiphyseal-hypothalamic interaction. An in vitro study with sheep pineal fractions, Experientia 29: 718.Google Scholar
  17. Collin, J.-P., 1979, Recent advances in pineal cytochemistry. Evidence of the production of indoleamines and proteinaceous substances by photoreceptor cells and pinealocytes of Amniota, Brain Res., 52: 271.CrossRefGoogle Scholar
  18. Collin, J.-P., 1981, New data and vistas on the mechanisms of secretion of proteins and indoles in the mammalian pinealocyte and its phylogenetic precursors; the pinealin hypothesis and preliminary comments on membrane traffic, in: “The Pineal Organ,” A. Oksche and P. Pévet, eds., Elsevier/North-Holland, Amsterdam-New York-Oxford.Google Scholar
  19. Collin, J.-P., and Oksche, A., 1981, in: “The Pineal Gland,” Vol. I, Anatomy and Biochemistry, R.J. Reiter, ed., CRC Press Inc., Boca Raton, Florida.Google Scholar
  20. Deguchi, T., 1981, Rhodopsin-like photosensitivity of isolated chicken pineal gland, Nature. 290: 706.PubMedCrossRefGoogle Scholar
  21. Ebels, I., 1979, A chemical study of some biologically active pineal fractions, Brain Res., 52: 309.CrossRefGoogle Scholar
  22. Ebels, I., 1981, Pteridines in the pineal organ, in: “The Pineal Organ,” A. Oksche and P. Pévet, eds., Elsevier/North-Holland, Amsterdam-New York-Oxford.Google Scholar
  23. Ebels, I., and Benson, B., 1978, A survey of the evidence that unidentified pineal substances affect the reproductive system in mammals, in: “The Pineal and Reproduction,” Progress in Reprod. Biol. Vol. 4, R.J. Reiter, ed., S. Karger, Basel.Google Scholar
  24. Ebels, I., and Horwitz-Bresser, A.E.M., 1976, Separation of pineal extracts by gelfiltration. IV. Isolation, location and identification from sheep pineals of three indoles identical with 5-hydroxytryptophol, 5-methoxytryptophol and melatonin, J. Neural Transm. 38: 31.PubMedCrossRefGoogle Scholar
  25. Ebels, I., Balemans, M.G.M., and Tommel, D.K.J., 1972a, Separation of pineal extracts on Sephadex G-10. III. Isolation and comparison of extracted and synthetic melatonin, Anal. Biochem. 50: 234Google Scholar
  26. Ebels, I., Balemans, M.G.M. and Verkleij, A.J., 1972b, Separation of pineal extracts on Sephadex G-10. II. A spectrofluorimetric and thin-layer chromatographic study of indoles in a sheep pineal extract, J. Neurovisc. Relat. 32:270.Google Scholar
  27. Ebels, I., Citharel, A., and Moszkowska, A., 1975, Separation of pineal extracts by gelfiltration. III. Sheep pineal factors acting either on the hypothalamus, or on the anterior hypophysis of mice and rats in in vitro experiments, J. Neural Transm. 36: 281.PubMedCrossRefGoogle Scholar
  28. Ebels, I., Moszkowska, A., and Scemama, A., 1965, Etude in vitro des extraits epiphysaires fractionnés. Résultats préliminaires, C.R. Acad. Sci. Paris 260:5126.Google Scholar
  29. Ebels, I., Moszkowska, A., and Scemama, A., 1970, An attempt to separate a sheep pineal extract fraction showing antigonadotropic activity J. Neurovisc. Relat. 32:1.Google Scholar
  30. Ebels, I., Benson, B., Bria, C.F., Richardson, D., Larsen, B.R., and Hruby, V.J., 1979, Location by paperchromatography of compensatory ovarian hypertrophy (COH) inhibiting activity in isobutanol extracts of bovine pineals, J. Neural Transm., 45: 43.PubMedCrossRefGoogle Scholar
  31. Frowein, A., and Lapin, V., 1979, Effects of sham-pinealectomy, performed under white and red light, on the melatonin content of the rat pineal glands, Experientia 35: 1681.PubMedCrossRefGoogle Scholar
  32. Fukushima, T., and Nixon, J.C., 1979, Reverse-phase high-performance liquid chromatographic separation of unconjugated pterins and pteridines, in: “Chemistry and Biology of Pteridines,” R.L. Kisliuk, and G.M. Brown, eds., North-Holland, Amsterdam.Google Scholar
  33. Fukushima, T., and Nixon, J.C., 1980, Analysis of reduced forms of biopterin in biological tissues and fluids, Anal. Biochem. 102:176.Google Scholar
  34. Hirst, B.H., Shaw, B., Meyers, C.A., and Coy, D.H., 1980, Structure-activity studies with somatostatin: The role of tryptophan in position 8, Reg. Peptides 1:97.Google Scholar
  35. Larsen, B.R., and Benson, B., 1979, Purification of bovine pineal prolactin inhibiting factor, Anal. Rec., 193: 598.Google Scholar
  36. Larsen, B.R., Benson, B., and Hruby, V.J., 1979, Synthesis and effects on prolactin of a bovine pineal tripeptide, in: “Peptides, Structure and Biological Function,”Pierce chemical co., Rockford, Illinois.Google Scholar
  37. Leadem, C.A., and Blask, D.E., 1982, A comparitive study of the effects of the pineal gland on prolactin synthesis, storage and release in male and female blind-anosmic rats, Biol. Reprod. 26:413.Google Scholar
  38. Martens, G.J.M., Jenks, B.G., and Van Overbeeke, A.P., 1981, Microsuperfusion of neurointermediate lobes of Xenopus laevis: Concomitant and coordinately controlled release of newly synthesized peptides, Ccmp. Biochem. Physiol. 69c:75.Google Scholar
  39. Matthews, M.J., and Benson, B., 1973, Inactivation of pineal antigonadotropin by proteolytic enzymes, J. Endocrinol. 56: 339.PubMedCrossRefGoogle Scholar
  40. Matthews, M.J., Benson, B., and Richardson, D.L., 1978, Partialmaintenance of testes and accessory organs in blinded hamsters by homoplastic anterior pituitary grafts or exogenous prolactin, Life Sci., 23: 1131.PubMedCrossRefGoogle Scholar
  41. Milcu, S., Milcu, J., and Nanu, L., 1963, Le Rôle de la glande pinéale dans le métabolisme des glucides, Ann. d’Endocr., 24: 233.Google Scholar
  42. Moszkowska, A., 1951, Contribution à l’etude de l’antagonismeépiphyso-hypophysaire, J. Physiol. Paris, 43: 827.Google Scholar
  43. Moszkowska, A., 1956, L’antagonisme épiphyso-hypophysaire. Etude in vitro par la méthode de E. Wolff, C.R. Acad. Sci., Paris, 243: 315.Google Scholar
  44. Moszkowska, A., 1958, Etude in vitro du röle de l’epiphyse dans l’excrétion d’hormones gonadotropes hypophysaires, C.R. Acad Sci., Paris, 247: 1659.Google Scholar
  45. Moszkowska, A., 1964, Quelques arguments en faveur de la spécificité zoologique de l’activité antigonadotrope de l’épiphyse, Ann. Endocr. 25 (suppl.): 79.Google Scholar
  46. Moszkowska, A., 1965, Contribution à l’étude du,mécanisme de l’antagonisme épiphyso-hypophysaire, Prog. Brain. Res., 10:564.Google Scholar
  47. Moszkowska, A., and Ebels, I., 1968, A study of the antigonadotropic action of synthetic arginine vasotocin, Experientia 24: 610.Google Scholar
  48. Moszkowksa, A., and Ebels, I., 1971, The influence of the pinealGoogle Scholar
  49. body on the gonadotropic function of the hypophysis, J. Neurovisc. Relat. Suppl 10:160.Google Scholar
  50. Moszkowska, A., and Heersche, J.N.M., 1962, in: “Int. Congr. Physiol. Sci.,” Leiden, No 518, Excerpta Med. Int. Congr. Series 48: X XII.Google Scholar
  51. Moszkowska, A., Scemama, A., Lombard, M.M., and Héry, t4., 1973) Experimental modulation of hypothalamic content of the gonado-tropic releasing factors by pineal factors in the rat, J. Neural. Transm. 34:11.Google Scholar
  52. Neacsu, C., 1972, Structure-activity data on a pineal peptide with oxytocic and vasopressor activities, Proc. Sci. Int. Sympo-sium, Liège, Sept. 28 - Oct. 1, 1971; Excerpta Med. Int. Congr. Series, No 241: 275.Google Scholar
  53. Neacsu, C., 1972, The mechanism of antigonadotropic action of a polypeptide extracted from a bovine pineal gland, Rev. Roum. Physiol. 9: 161.PubMedGoogle Scholar
  54. Noteborn, H.P.J.M., Ebels, I., Pévet, P., Reinharz, A.C., Neacsu, C., and Salemink, C.A., 1982, Comparison of some peptidic and proteic ovine pineal fractions with a bovine pineal E5 fraction, J. Neural Transm. in press.Google Scholar
  55. Orts, R.J., Laio, T.-H., Sartin, J.L., and Bruot, B., 1978, Purification of a tripeptide with anti-reproductive properties isolated from bovine pineal glands, Physiologist 21: 87.Google Scholar
  56. Ota, M., Horiuchi, S., and Obara, K., 1975, Inhibition of ovulation induced with PMS and HCG by a melatonin-free extract of bovine pineal powder, Neuroendocrinology 18: 311.Google Scholar
  57. Pavel, S., 1979, The mechanism of action of vasotocin in the mammalian brain, Progr. Brain Res., 52: 445.CrossRefGoogle Scholar
  58. Pévet, P., 1979, Secretory processes in the mammalian pinealocyte under natural and experimental conditions, Progr. Brain Res., 52: 149.CrossRefGoogle Scholar
  59. Pévet, P., 1981a, Ultrastructure of the mammalian pinealocytes,in: “The Pineal Gland,” Vol. I, Anatomy and Biochemistry, R.J. Reiter, ed., CRC Press, Boca Raton, Florida.Google Scholar
  60. Pévet, P., 1981b, Peptides in the pineal gland of vertebrates. Ultra-structural, histochemical, immunocytochemical and radioimmunological aspects, in: “The Pineal Organ,” A. Oksche, and P. Pévet, eds., Elsevier/North-Holland, Amsterdam-New York-Oxford.Google Scholar
  61. Pévet, P., 1982a, Pineal peptides in the fetus and in young and adult mammals, in: “Melatonin Rhythm,” D.C. Klein, ed., S. Karger, Basel, in press.Google Scholar
  62. Pévet, P., 1982b, The anatomy of the pineal gland of mammals, in: “The Pineal Gland,” R. Relkin, ed., Elsevier/North-Holland, New York, in press.Google Scholar
  63. Pévet, P., Ebels, I., Swaab, D.F., Mud, M.T., and Arimura, A., 1980, Presence of AVT-, Cr,-MSH-, LHRH- and somatostatin-like compounds in the rat pineal gland and their relationship with the UMO5R pineal fraction, Cell. Tiss. Res. 206:341.Google Scholar
  64. Rajh, H.M., Smyth, M.J., Renckers, B.A.M., Jansen, J.W.C.M., De Pont, J.J.H.H.M., Bonting, S.L., Tesser, G.J., and Nivard, R.J.F., 1980, Role of the tryptophan residue in the interaction of pancreazymin with its receptor, Biochim. Biophys. Acta 632: 386Google Scholar
  65. Reiss, M., Davis, R.H., Sideman, M.B., Mauer, I., and Plichta, E.S., 1963a, Action of pineal extracts on the gonads and their function, J. Endocr. 27: 107.Google Scholar
  66. Reiss, M., Mauer, I., Sideman, M.B., Davis, R.H., and Plichta, E.S., 1963b, Pituitary-pineal-brain interrelationships, J. Neurochem. 10: 851.PubMedCrossRefGoogle Scholar
  67. Reiter, R.J., 1980, “The Pineal Gland,” Vol. 5, Eden Press Inc., St. Albans, U.S.A.Google Scholar
  68. Reiter, R.J., 1981, “The Pineal Gland,” Vol. 6, Eden Press Inc., St. Albans, U.S.A.Google Scholar
  69. Reiter, R.J., and Ferguson, B.N., 1979, Delayed reproductive regression in male hamsters bearing intrarenal homografts and kept under natural winter periods, J. Exp. Zool. 209:175.Google Scholar
  70. Slama-Scemama, A., L’Héritier, A., Moszkowska, A., Van der Horst, C.J.G., Noteborn, H.P.J.M., De Morée, A., and Ebels, I., 1979, Effects of sheep pineal fractions on the activity of male rat hypothalami in vitro J. Neural Transm. 46: 47.Google Scholar
  71. Smith, A.R., and Ariens Kappers, J., 1975, Effect of pinealectomy, gonadectomy, p-CPA and pineal extracts on the rat parvocel-lular neurosecretory hypothalamic system; a fluorescence histochemical investigation, Brain Res., 86: 353.PubMedCrossRefGoogle Scholar
  72. Sorrentino, S. jr., 1968, Antigonadotropic effects of melatonin in intact and unilaterally ovariectomized rats, Anat. Rec., 160: 432.Google Scholar
  73. Thiéblot, L., and Thiéblot, Ph., 1981, “La Gland Pinéale,” ? Physiologie et Clinique, S.A. Maloine, ed., Paris.Google Scholar
  74. Vaughan, M.K., 1981, Arginine vasotocin and vertebrate reproduction, in: “The Pineal Gland,” Vol. II, Reproductive Effects, R.J. Reiter, ed., CRC Press, Boca Raton, Florida.Google Scholar
  75. Vaughan, M.K., and Blask, D.E., 1978, Arginine vasotocin - A search for its function in mammals, in: “The Pineal and Reproduction,” Progress in Reproductive Biology, Vol. 4., R.J. Reiter, ed., S. Karger, Basel.Google Scholar
  76. Vaughan, M.K., Johnson, L.Y., Pévet, P., Neacsu, C., and Reiter, R.J., 1980, Effect of a polypeptide (E5) extracted from bovine pineal glands on plasma and pituitary levels of luteinizing hormone (LH) and prolactin in normal and castrated adult male rats. Tenth Ann. Mtg., Soc. Neurosci. 16:457.Google Scholar
  77. Vaughan, M.K., Richardson, B.A., Johnson, L.Y., Reiter, R.J., Privet, P., and Neacsu, C., 1982, Effects of a bovine pineal peptidic fraction (E5) on plasma and pituitary levels of LH, FSH and prolactin, Experientia, in press.Google Scholar
  78. Zurburg, W., and Ebels, I., 1974, Separation of pineal extracts by gel filtration. I. Isolation from sheep pineals of a substance with special fluorescence characteristics, J. Neural Transm. 35: 117.PubMedCrossRefGoogle Scholar
  79. Zurburg, W., and Ebels, I., 1975, Separation of pineal extracts by gel filtration. II. Identification and isolation of two indoles from sheep pineal glands, J. Neural Transm. 36: 59.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1983

Authors and Affiliations

  • I. Ebels
    • 1
  1. 1.Department of Organic ChemistryState University of UtrechtThe Netherlands

Personalised recommendations