Molecular Aspects of Neuroendocrine Integrative Processes in the Pineal Gland

  • D. P. Cardinali
  • Mónica N. Ritta
  • María I. Vacas
  • P. R. Lowenstein
  • P. V. Gejman
  • C. González Solveyra
  • Elba Pereyra
Part of the NATO Advanced Science Institutes Series book series (NSSA, volume 65)


The mammalian pineal gland fulfills the criteria of a “neuroendocrine” transducer.1 It translates a neural language provided by norepinephrine (NE) released at the synaptic biophase to a hormone language,melatonin and perhaps endocrine active peptides. The pinealocytes are also “endocrineendocrine” transducers inasmuch as they convert an endocrine language, e.g. estradiol attaining the gland via the general circulation, to a different endocrine signal like melatonin. Additionally “endocrine-neural” transducer events occur in the pineal gland, as revealed by the significant modifications of the activity of the innery ting sympathetic pathway after several hormone treatments.1,2


Pineal Gland Superior Cervical Ganglion Pineal Organ Pineal Protein Melatonin Synthesis 
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. 1.
    R.J.Wurtman, Neuroendocrine transducers and monoamines Fed. Proc. 32: 1769 (1973).PubMedGoogle Scholar
  2. 2.
    D.P.Cardinali, Molecular mechanisms of neuroendocrine integration in the central nervous system: An approach through the study of the pineal gland and its innervating sympathetic pathway, Psychoneuroendocrinology in press.Google Scholar
  3. 3.
    R.T.Moore, The innervation of the mammalian pineal gland, Proq. Reprod. Biol., 4: 1 (1978).Google Scholar
  4. 4.
    M.Brownsteín and J.Axelrod, Pineal gland: 24-hour rhythm in norepinephrine turnover, Science, 148: 163 (1974).CrossRefGoogle Scholar
  5. 5.
    H.Nishino, K.Koizumi and C.Mc C.Brooks, The role of suprachiasmatic nuclei of the hypothalamus in the production of circadian rhythms, Brain Res, 112: 4 (1975).Google Scholar
  6. 6.
    D.C.Klein, G.R.Berg and J.L.Weller, Melatonin synthesis: Adenosine 35-monophosphate and norepinephrine stimulate N-acetyltransferase, Science, 168: 979 (1970).PubMedCrossRefGoogle Scholar
  7. 7.
    R.J.Wurtman, H.M.Shein and F.Larin, Mediation by β -adrenergic receptors of effect of no epinephrine on pineal synthesis of 14C serotonin and 140 melatonin, J. Neurochem, 18: 1683 (1971).PubMedCrossRefGoogle Scholar
  8. 8.
    M.Zatz, Sensitivity and cyclic nucleotides in the rat pineal gland, J. Neural Transm, Suppl. 13: 97 (1978)PubMedGoogle Scholar
  9. 9.
    W.Lovenberg and J.J.Morrisey, Synthesis of RNA in pineal gland during serotonin-N-acetyltransferase induction, Biochem. Pharmacol., 27: 551 (1978).PubMedCrossRefGoogle Scholar
  10. 10.
    W.Lovenberg and J.J.Morrisey, Protein synthesis in pineal gland during serotonin-N-acetyltransferase induction, Arch. Biochem. Biophys, 191: 1 (1978).PubMedCrossRefGoogle Scholar
  11. 11.
    F.Pelayo, M.L.Dubocovich and S.Z.Langer, Possible role of cyclic nucleotides in regulation of noradrenaline release from rat pineal through presynaptic adrenoceptors, Nature, 274: 76 (1978).PubMedCrossRefGoogle Scholar
  12. 12.
    H.J.Lynch, M.Ho and R.J.Wurtman, The adrenal medulla may mediate the increase in pineal melatonin synthesis induced by stress, but not that caused by exposure to darkness, J. Neural Transm. 40: 87 (1977).PubMedCrossRefGoogle Scholar
  13. 13.
    D.C.Klein and J.Weller, Adrenergic-adenosine 3,5-monophosphate regulation of serotonin-N-acetyltransferase activity to synthesis of 3H-N-acetylserotonin and 3Hmeletonin in the cultured rat pineal gland, J. Pharmacol. Exp. Ther., 189: 516 (1973).Google Scholar
  14. 14.
    L.Alphs, A.Heller and W.Lovenberg, Adrenergic regulation of the reduction in acetyl coenzyme A: arylamine Nacetyltransferase activity in the rat pineal, J. Neurochem., 34: 83 (1980).PubMedCrossRefGoogle Scholar
  15. 15.
    T.L.Smith, J.Eichberg and G.Hanser, Postsynaptic localization of the alpha receptor-mediated stimulation of phosphatidylinositol turnover in pineal gland, Life Sci., 24: 2179 (1979).PubMedCrossRefGoogle Scholar
  16. 16.
    F.Pelayo, M.L.Dubocovich and S.Z.Langer, Regulation of noradrenaline release in the rat pineal gland through a negative feedback mechanism mediated by presynaptic ckadrenoceptors, Eur. J. Pharmacol., 45: 317 (1977).Google Scholar
  17. 17.
    M.I.Vacas, P.R.Lowenstein and D.P.Cardinali, Dihydroergocryptine binding sites in bovine and rat pineal glands, J. Auton. Nerv. System, 2: 305 (1980).CrossRefGoogle Scholar
  18. 18.
    D.C.Klein, D.A.Auerbach, M.A.A.Namboodiri, G.H.T.Wheler, Indole metabolism in the mammalian pineal gland, in: “The Pineal Gland. Vol. I. Anatomy and Biochemistry”, R.J.Reiter, ed., CRC Press, Boca Raton, Fla. (1981), p. 199.Google Scholar
  19. 19.
    M.J.Berridge, Phosphatidylinositol hydrolysis: A multifunctional transducing mechanism, Mol. Celi. Endocr., 24: (1981).Google Scholar
  20. 20.
    E.G.Lapetina, Regulation of arachidonic acid production: Role of phosphalipases C and A2, Trends Pharmacol. Sci., 3: 115 (1982).CrossRefGoogle Scholar
  21. 21.
    L.S.Wolfe, Eicosanoids: Prostaglandins, thromboxanes, leukotrienes and other derivatives of carbon-20 unsaturated fatty acids, J. Neurochem., 38: 1 (1982).PubMedCrossRefGoogle Scholar
  22. 22.
    T.C.Westfall, Neuroeffector mechanisms, Annu. Rev. Physiol., 42: 383 (1980).PubMedCrossRefGoogle Scholar
  23. 23.
    R.Szabo and A.J.Friedhoff, Decrease of serotonin-N-acetyltransferase activity in rat pineal organs after treatment with prostaglandin synthesis inhibitor indomethacin, Prostaglandins, 11: 503 (1976).PubMedGoogle Scholar
  24. 24.
    M.N. Ritta and D.P. Cardinali, Effect of indomethacin treatment on monoamine metabolism and melatonin synthesis of rat pineal gland, Hormone Res., 12: 305 (1980).PubMedCrossRefGoogle Scholar
  25. 25.
    N.H.Neff and H.Y.Yang, Another look at the monoamine-oxidase inhibitor drugs, Life Sci., 14: 2061 (1974).PubMedCrossRefGoogle Scholar
  26. 26.
    M.I.Uacas and D.P.Cardinali, Effects of castration and reproductive hormones on pineal serotonin metabolism in rats, Neuroendocrinology, 28: 187 (1979).CrossRefGoogle Scholar
  27. 27.
    R.Flowers, Drugs which inhibit prostaglandin synthesis, Pharmacol. Rev., 26: 33 (1974).Google Scholar
  28. 28.
    H.S.Kantor and M.Hampton, Indomethacin in submicromolar concentrations inhibits cyclic AMP dependent protein kinase, Nature, 276: 841 (1978).PubMedCrossRefGoogle Scholar
  29. 29.
    D.P.Cardinali, M.N.Ritta, N.S.Speziale and M.F.Gimeno, Release and specific binding of prostaglandins in bovine pineal gland, Prostaglandins, 18: 577 (1979).PubMedGoogle Scholar
  30. 30.
    M.Mglller and Th. van Veen, Fluorescence histochemistry of the pineal gland, in:“The Pineal Gland. Uol.I Anatomy and Biochemistry”, R.J.Reiter, ed., CRC Press, Boca Raton Fla (1981) p. 69.Google Scholar
  31. 31.
    M.N.Ritta and D.P.Cardinali, Prostaglandin E2 increases adenosine 3,5-monophosphate.concentration and binding site occupancy, and stimulates serotonin-N-acetyltransferase activity in rat pineal glands in vitro, Mol. Cell. Endocr., 23: 151 (1981).CrossRefGoogle Scholar
  32. 32.
    D.P.Cardinali, M.N.Ritta, C.Gonzalez Solveyra and E. Pereyra, Role of prostaglandins in rat pineal neuroeffector junction. Changes in melatonin and norepinephrine release in vitro, Endocrinology, in press.Google Scholar
  33. 33.
    S.Suzuki, R.Franco-Saenz and P.J.Mulrow, The role of renal prostaglandins in the renin response to isoproterenol in the rat in vitro, Endocrinology, 108: 1654 (1981).PubMedCrossRefGoogle Scholar
  34. 34.
    C.R.Partington, M.W.Edwards and J.W.Daly, Regulation of cyclic AMP formation in brain tissue by α-adrenergic receptors: Requisite intermediacy of prostaglandins of the E series, Proc. Nat. Acad. Sci. USA, 77: 3024 (1980).PubMedCrossRefGoogle Scholar
  35. 35.
    P.Hedqvist, Basic mechanisms of prostaglandin action on autonomic neurotransmission, Annu. Rev. Pharmacol. Toxicol. 17: 249 (1977).CrossRefGoogle Scholar
  36. 36.
    S.Hirose, H.Yokosawa, I.Inagami and J.Workman, Renin and prorenin in hog brain: ubiquitous distribution and high concentration in the pituitary and pineal, Brain Res., 191: 489 (1980).PubMedCrossRefGoogle Scholar
  37. 37.
    D.G.Changaris, L.M.Demers, L.C.Keil and W.B.Severs, Immunopharmacology of angiotensin I in brain, in: “Central Actions of Angiotensin and Related Hormones” J.P. Buckley and C.Ferraro, eds., Pergamon, New York (1977) p 233.Google Scholar
  38. 38.
    D.G.Changaris, L.C.Keil and W.B.Severs, Angiotensin II immunohistochemistry of the rat brain, Neuroendocrinology, 25: 257 (1978).PubMedCrossRefGoogle Scholar
  39. 39.
    N.M.Panagiotis and G.F.Hungerford, Response of pineal sympathetic nerve processes and endings to angiotensin, Nature, 211: 374 (1966).PubMedCrossRefGoogle Scholar
  40. 40.
    I.Haulica, G.Petrescu, M.Ulnitu, V.Rasca and S.Slatineanus, Influence of angiotensin II on dog pineal serotonin content, Neurosci. Lett., 18: 329 (1980).PubMedCrossRefGoogle Scholar
  41. 41.
    B.Chertow, The role of lysosomes and proteases in hormone secretion and degradation, Endocr. Rev. 2: 137 (1981).PubMedCrossRefGoogle Scholar
  42. 42.
    V.E.Nahmod,M.S.Bwlda, C.J.Pirola, S.Finkielman, P.U.Gejman and D.P.Cardinali, Circadian rhythm and neural regulation of rat pineal angiotensin converting enzyme, Brain Res. 236: 216 (1982).PubMedCrossRefGoogle Scholar
  43. 43.
    V.E.Nahmod, E.F.Lazcano, C.J.Pirola, M.S.Balda, A.Alvarez, P.U.Gejman and D.P.Cardinali, Efecto inhibitorio del simpético sobre la actividad del sistema renina-angiotensina en la pineal de la rata, Medicina (Buenos Aires) 40: 770 (1980) (abs).Google Scholar
  44. 44.
    M.J.Peach, Renin-angiotensin system: Biochemistry and mechanisms of action, Physiol. Rev., 57: 313 (1977).PubMedGoogle Scholar
  45. 45.
    P.V.Gejman, D.P.Cardinali, S.Finkielman and V.E.Nahmod, Changes in drinking behavior caused by superior cervical ganglionectomy and pinealectomy in rats, J. Auton. Nerv. System, 4: 249 (1981).CrossRefGoogle Scholar
  46. 46.
    D.P.Cardinali, Hormone effects on the pineal gland, in: “The Pineal Gland. Vol.I. Anatomy and Biochemistry”, R.J.Reiter, ed., CRC Press, Boca Raton Fla (1981) p 243.Google Scholar
  47. 47.
    D.P.Cardinali, C.A.Nagle and J.M.Rosner, Control of estrogen and androgen receptors in the rat pineal gland by catecholamine transmitter, Life Sci. 16: 93 (1975).PubMedCrossRefGoogle Scholar
  48. 48.
    D.P.Cardinali, C.A.Nagle and J.M.Rosner, Metabolic fate of androgens in the pineal organ: Uptake, binding to cytoplasmic proteins and conversion of testosterone into 5α-reduced metabolites, Endocrinology, 95: 179 (1974).PubMedCrossRefGoogle Scholar
  49. 49.
    M.I.Vacas, P.R.Lowenstein and D.P.Cardinali, Characterization of a cytosolprogesterone receptor in bovine pineal gland, Neuroendocrinology, 24: 84 (1979).CrossRefGoogle Scholar
  50. 50.
    M.I.Vacas and D.P.Cardinali, Binding sites for melatonin in bovine pineal gland, Hormone Res., 13: 121 (1980).PubMedCrossRefGoogle Scholar
  51. 51.
    W.E.Stumpf and M.Sar, Steroid hormone target cells in the periventricular brain: Relationship to peptide hormone producing cells, Fed. Proc., 36: 1973 (1977).PubMedGoogle Scholar
  52. 52.
    D.P.Cardinali, C.A.Nagle and J.M.Rosner, Aromatization of androgens to estrogens by the rat pineal gland, Experientia, 30: 1222 (1974).PubMedCrossRefGoogle Scholar
  53. 53.
    D.P.Cardinali, C.A.Nagle and J.M.Rosner, Gonadal steroids as modulators of the function of the pineal gland, Gen. Comp. Endocr., 26: 50 (1975).PubMedCrossRefGoogle Scholar
  54. 54.
    I.Hahukoglu, H.J.Karavolas and R.W.Goy, Progesterone metabolism in the pineal gland, brain stem, thalamus and corpuscallosum of the female rat, Brain Res., 125: 313 (1977).CrossRefGoogle Scholar
  55. 55.
    G.Litwack, ed. “Biochemical Actions of Steroids”, val. 6, Academic Press, New York (1979).Google Scholar
  56. 56.
    E.U.Jensen, M.Numata, P.I.Brecher and E.R.De Sombre, Hormone-receptor interaction as a guide to biochemical mechanism, in: “The Biochemistry of Steroid Hormone Action”, R.M.S. Smellie, ed., Academic Press, New York (1971) p. 133.Google Scholar
  57. 57.
    M.Ginsburg, B.D.Greenstein, N.J.MacLusky and P.J.Thomas, An improved method for the study of high affinity steroid binding: Oestradiol binding in the brain and pituitary, Steroids, 23: 773 (1974).PubMedGoogle Scholar
  58. 58.
    D.P.Cardinali, Nuclear receptor-estrogen complex in the pineal gland. Modulation by sympathetic nerves, Neuroendocrinology, 24: 333 (1977).PubMedCrossRefGoogle Scholar
  59. 59.
    I.Lieberburg, N.MacLusky and B.S.McEwen, Cytoplasmic and nuclear estradiol-17β binding in male and female rat brain: Regional distribution, temporal aspects and metabolism, Brain Res., 193: 487 (1980).PubMedCrossRefGoogle Scholar
  60. 60.
    T.G.Muldoon, Regulation of steroid hormone activity, Endocr. Rev., 1: 339 (1980).PubMedCrossRefGoogle Scholar
  61. 61.
    D.P.Cardinali, E.Gomez and J.M.Rosner, Changes in 3H-leu-cine incorporation into pineal proteins following estradiol or testosterone administration: Involvement of the sympathetic superior cervical ganglion, Endocrinology, 94: 849 (1976).CrossRefGoogle Scholar
  62. 62.
    N.Emmelin and U.Trendelenburg, Degeneration activity after parasympathetic or sympathetic denervation, Rev. Physiol. Biochem. Exp. Pharmacol., 66: 148 (1972).Google Scholar
  63. 63.
    P.Schotman, J.Allart and W.H.Gispen, Pineal protein synthesis highly sensitive to ACTH-like neuropeptides, Brain Res., 219: 121 (1981).PubMedCrossRefGoogle Scholar
  64. 64.
    C.A.Nagle, D.P.Cardinali and J.M.Rosner, Testosterone effects on protein synthesis in the rat pineal gland. Modulation by the sympathetic nervous system, Life Sci., 16: 81 (1975).PubMedCrossRefGoogle Scholar
  65. 65.
    C.A.Nagle, D.P.Cardinali and J.M.Rosner Diurnal rhythm in tissue radioactivity uptake after 3-H-estradiol and 3H-testosterone administration to castrated rats, Steroids Lip. Res., 5: 107 (1974).Google Scholar
  66. 66.
    P.Seem, C.Demaine and L.Uollrath, The effects of sex hormones,prolactin and chorionic gonadotrophin on pineal electrical activity in guinea pigs. Cell. Mol. Neurobiol. 1: 259 (1981).CrossRefGoogle Scholar
  67. 67.
    J.T.Epplen, H.Kaltenhauser, W.Engel and J.Schmidtke, Patterns of cyclic AMP phosphodiesterases in the rat pineal gland: Sex differences in diurnal rhythmicity, Neuro-endocrinology, 34: 46 (1982).Google Scholar
  68. 68.
    D.P.Cardinali, C.A.Nagle, E.Gomez and J.M.Rosner, Norepinephrine turnover in the rat pineal gland. Acceleration by estradiol and testosterone, Life Sci., 16: 1717 (1975).PubMedCrossRefGoogle Scholar
  69. 69.
    D.P.Cardinali and M.I.Uacas, Norepinephrine turnover in pineal gland and superior cervical ganglia. Changes after gonadotrophin administration to castrated rats, J. Neural Transm. 45: 273 (1979).PubMedCrossRefGoogle Scholar
  70. 70.
    D.P.Cardinali, M.I.Uacas and P.U.Gejman, The sympathetic superior cervical ganglia as peripheral neuroendocrine centers, J. Neural. Transm., 52: 1 (1981).PubMedCrossRefGoogle Scholar
  71. 71.
    M.I.Uacas, P.R.Lowenstein and D.P.Cardinali, Testosterone decreases β-adrenoceptor sites in rat pineal gland and brain, J. Neural Transm. 53: 49 (1982).CrossRefGoogle Scholar
  72. 72.
    M.I.Uacas and D.P.Cardinali, Effect of estradiol on and β-adrenoceptor density in medial basal hypothalamus, cerebral cortex and pineal gland of ovariectomized rats, Neurosci. Lett., 17: 73 (1980).CrossRefGoogle Scholar
  73. 73.
    D.P.Cardinali, M.I.Uacas, C.E.Ualenti and C.Gonzalez Solveyra, Pineal gland and sympathetic cervical ganglia as sites for steroid regulation of photosensitive neuro-endocrine pathways, J. Steroid Biochem., 11: 951 (1979).PubMedCrossRefGoogle Scholar
  74. 74.
    L.T.Williams and R.J.Lefkowitz, “Receptor Binding Studies in Adrenergic Pharmacology”, Raven Press, New York (1978).Google Scholar
  75. 75.
    D.P.Cardinali, M.I.Uacas, A.L.Fortis and F.J.Stefano, Superior cervical ganglionectomy depresses norepinephrine uptake, increases the density of α-adrenoceptor sites and induces supersensitivity to adrenergic drugs in rat medial basal hypothalamus, Neuroendocrinology, 33: 199 (1981).PubMedCrossRefGoogle Scholar
  76. 76.
    M.Pisarev, D.P.Cardinali, G.Juvenal, M.I.Uacas, M.Barontini and R.Boado, The role of the sympathetic nervous system in the control of the goitrogenic response in the rat. Endocrinologj, 109: 2202 (1981).CrossRefGoogle Scholar
  77. 77.
    D.P.Cardinali, M.Pisarev, M.Barontini, G.Juvenal, R.Boado and M.I.Uacas, Efferent neuroendocrine pathways of sympathetic superior cervical ganglia. Early inhibition of pituitary-thyroid axis after ganglionectomy, Neuroendocrinology, in press.Google Scholar

Copyright information

© Springer Science+Business Media New York 1983

Authors and Affiliations

  • D. P. Cardinali
    • 1
  • Mónica N. Ritta
    • 1
  • María I. Vacas
    • 1
  • P. R. Lowenstein
    • 1
  • P. V. Gejman
    • 1
  • C. González Solveyra
    • 1
  • Elba Pereyra
    • 1
  1. 1.Centro de Estudios Farmacológicos y de Principios Naturales (CEFAPRIN)Buenos AiresArgentina

Personalised recommendations