Summary
The morphological effects of colchicine on the entire neurosecretory (NS) tract and on various hypothalamic nuclei have been studied. The perturbation in axonal flow, indicated by the accumulation of NS material, coincide with fragmentation of the cytoplasmic membranes, i. e. the Golgi apparatus and the endoplasmic reticulum, whereas the neurotubules remain relatively well preserved. Autophagic destruction of NS material is observed along the entire length of the NS fibres. The rapid and systematic changes in the axoplasmic reticulum, known to store calcium, lead us to envisage a role for this system — similar to that of the sarcoplasmic reticulum — in controlling the transport of NS vesicles. The junctional zone between the stalk and the neural lobe seems to play a particular rôle in the transport of NS material to the posthypophysial terminals of the NS axons. Colchicine provokes an increase in dense-cored vesicles in most of the neurons of the other hypothalamic nuclei studied: arcuate, suprachiasmatic, periventricular and ventromedial. Membranous alterations are also observed in these sites. Colchicine administered to animals which were hypothyroid, castrated or adrenalectomized, reveals stimulated neurons, identified by their excessive content of dense-cored vesicles. These neurons display no specific localization, for they occur in all hypothalamic nuclei, irrespective of the stimulation. The frequency of stimulation of neurons of the periventricular nucleus is striking.
Similar content being viewed by others
References
Albe Fessard, D., Stutinsky, F., Libouban, S.: Atlas stéréotaxique du diencéphale du rat blanc. Eds. CNRS CNRS Paris, 1971
Barry, J., Dubois, M.P., Poulain, P.: LRF producing cells of the mammalian hypothalamus. Z. Zellforsch. 146, 351–366 (1973)
Berens, S.C., Williams, J.A., Wolff, J.: Dissociation of thyrotropin stimulated hormone secretion and glucose oxidation in thyroid glands by lithium and colchicine. Biochim. biophys. Acta (Amst.) 252, 314–323 (1971)
Berl, S., Puszkin, S.: Mg2+-Ca2+ activated adenosine triphosphatase system isolated from mammalian brain. Biochemistry (Wash.) 9, 2058–2067 (1970)
Berl, S., Puszkin, S., Nicklas, W.J.: Actomyosin-like protein in brain. Actomyosin-like protein may function in the release of transmitter material at synaptic endings. Science 179, 441–446 (1973)
Björklund, A., Nobin, A.: Fluorescence and microspectrofluorometric mapping of dopamine and noradrenaline cell groups in the rat diencephalon. Brain Res. 51, 193–205 (1973)
Borisy, G.G., Taylor, E.W.: The mechanism of action of colchicine. Binding of colchicine 3-H to cellular protein. J. Cell Biol. 34, 525–543 (1967)
Boudier, J.A.: Autophagie du matériel neurosécrétoire dans le lobe postérieur de l'hypophyse du rat au début de la réhydratation. C.R. Acad. Sci. (Paris) 278, 2959–2962 (1974)
Boudier, J.A., Detieux, Y.: Effets de la colchicine sur la recharge en neurosecrétat de la neurohypophyse du rat après déplétion par privation d'eau. J. Neurovisc. Relat. 32, 282–297 (1972)
Brawer, J.R.: The role of the arcuate nucleus in the brain-pituitary-gonad axis. J. comp. Neurol. 143, 411–446 (1971)
Byers, M.R.: Structural correlates of rapid axonal transport. Evidence that microtubules may not be directly involved. Brain Res. 75, 97–113 (1974)
Byers, M.R., Hendrickson, A.E., Finck, B.R., Kennedy, R.D., Middaugh, M.E.: Effects of lidocaine on axonal morphology, microtubules, and rapid transport in rabbit vagus nerve in vitro. J. Neurobiol. 4, 125–144 (1973)
Chang, C.M.: Effect of colchicine and cytochalasine B on axonal particle movement and outgrowth in vitro. J. Cell Biol. 55, 37A (1972)
Dahl, D.R., Redburn, D.A., Samson, F.E. Jr.: Regional distribution of colchicine binding (microtubular) protein in the rat brain. J. Neurochem. 17, 1215–1219 (1970)
Dahlström, A.: Effect of colchicine on transport of amine storage granules in sympathetic nerves of rat. Europ. J. Pharmacol. 5, 111–113 (1968)
Davidson, P.F., Winslow, B.: The protein subunit of calf brain neurofilament. J. Neurobiol. 5, 119–133 (1974)
Dellmann, H.-D.: Degeneration and regeneration of neurosecretory systems. Int. Rev. Cytol. 36, 215–315 (1973)
De Meis, L., Rabin-Aetschal, B.M., Machado, R.D.: Comparative data of Ca++ transport in brain and skeletal muscle microsomes. J. biol. Chem. 245, 1883–1889 (1970)
Douglas, W.W., Ishida, A., Poisner, A.M.: The effect of metabolic inhibitors on the release of vaso-pressin from the isolated neurohypophysis. J. Physiol. (Lond.) 181, 753–759 (1965)
Douglas, W.W., Poisner, A.M.: Stimulus secretion coupling in a neurosecretory organ: the role of calcium in the release of vasopressin from the neurohypophysis. J. Physiol. (Lond.) 172, 1–18 (1964)
Douglas, W.W., Sorimachi, M.: Colchicine inhibits adrenal medullary secretion evoked by acetyl choline without affecting that evoked by potassium. Brit. J. Pharmacol. 45, 129–132 (1972a)
Douglas, W.W., Sorimachi, M.: Effects of cytochalasin and colchicine on secretion of posterior pituitary and adrenal medullary hormones. Brit. J. Pharmacol. 45, 143–144 (1972b)
Droz, B., Koenig, H.L., Rambourg, A. Transport intracytoplasmique de macromolécules et réticulum endoplasmique lisse: cas du flux axonal rapide. J. Microsc. (Paris) 20, 45a (1974)
Droz, B., Rambourg, A., Koenig, H.L.: The smooth endoplasmic reticulum; structure and role in the renewal of axonal membrane and synaptic vesicles by fast axonal transport. Brain Res. 93, 1–13 (1975)
Dustin, P., Hubert, J.P., Flament-Durand, J.: Action of colchicine on axonal flow and pituicytes in the hypothalamo-pituitary system of the rat. Ann. N.Y. Acad. Sci. 253, 670–684 (1975)
Edwards, J.C., Howell, S.L.: Effects of vinblastine and colchicine on the secretion of glucagon from isolated guinea-pig islets of Langerhans. FEBS Lett. 30, 89–91 (1973)
Feit, H., Barondes, H.: Colchicine binding activity in particulate fractions of mouse brain. J. Neurochem. 17, 1355–1363 (1970)
Feit, H., Dutton, G.R., Barondes, H., Shelanski, M.L.: Microtubule protein. Identification and transport to nerve endings. J. Cell Biol. 51, 138–147 (1971)
Fernandez, H.L., Burton, P.R., Samson, F.E.: Axoplasmic transport in the crayfish nerve cord. The role of fibrillar constituents of neurons. J. Cell Biol. 51, 176–192 (1971)
Fine, R.E., Blitz, A.L., Hitchcock, S.E., Kaminer, B.: Tropomyosin in brain and growing neurones. Nature (Lond.). New Biol. 245, 182–186 (1973)
Fine, R.E., Bray, P.: Actin in growing nerve cells. Nature (Lond.). New Biol. 234, 115–118 (1971)
Flament-Durand, J., Dustin, P.: Studies on the transport of secretory granules in the magnocellular hypothalamic neurones. I. Action of colchicine on axonal flow and neurotubules in the paraventricular nuclei. Z. Zellforsch. 130, 440–445 (1972)
Gautvik, K.M., Tashjian, A.H. Jr.: Effects of cations and colchicine on the release of prolactine and growth hormone by functional pituitary tumor cells in culture. Endocrinology 93, 793–799 (1973)
Gillespie, E.: Microtubules, cyclic AMP, calcium and secretion. Ann. N.Y. Acad. Sci. 253, 771–779 (1975)
Gillespie, E., Levine, R.J., Malawista, S.E.: Histamine release from rat peritoneal mast cells: inhibition by colchicine and potentiation by deuterium oxide. J. Pharmacol. exp. Ther. 164, 158–165 (1968)
Grainger, F., Sloper, J.C.: Correlation between microtubular number and transport activity of hypothalamo-neurohypophysial secretory neurons. Cell Tiss. Res. 153, 101–113 (1974)
Hindelang-Gertner, C., Stoeckel, M.E., Porte, A., Dellmann, H.-D., Madarasz, B.: Nematosomes or nucleolus-like bodies in hypothalamic neurons, the subfornical organ and adenohypophysial cells of the rat. Cell Tiss. Res. 155, 211–219 (1974)
Hökfelt, T., Dahlström, A.: Effects of two mitosis inhibitors (colchicine and vinblastine) on the distribution and axonal transport of noradrenaline storage particles, studied by fluorescence and electron microscope. Z. Zellforsch. 119, 460–482 (1971)
Inoué, S., Sato, H.: Cell motility by labile association of molecules. J. gen. Physiol. 50, (Suppl.) 259–292 (1967)
Ishikawa, H., Bischoff, R., Holther, H.: Formation of arrowhead complex with heavy meromyosin in a variety of cell types. J. Cell Biol. 43, 312–328 (1969)
Joly, L., Joly, P., Porte, A., Girardie, A.: Etude physiologique et ultrastructurale des corpora allata de Locusta migratoria (Orthoptére) en phase grégaire. Arch. Zool. Exp. Gén. 109, 703–728 (1968)
Kaminer, B., Kimura, J.: Deuterium oxide: inhibition of calcium release in muscle. Science 176, 406–407 (1972)
Karlsson, J.-O., Hansson, H.-A., Sjöstrand, J.: Effect of colchicine on axonal transport and morphology of retinal ganglion cells. Z. Zellforsch. 115, 265–283 (1971)
Kirkpatrick, J.B., Bray, J.J., Palmer, S.M.: Visualization of axoplasmic flow in vitro by Nomarksi microscopy. Comparison of rapid flow of radioactive proteins. Brain Res. 43, 1–10 (1972)
Klein, M.J., Stoeckel, M.E., Porte, A., Stutinsky, F.: Sur les modifications ultrastructurales des cellules neurosécrétoires hypothalamiques (Noyaux SO et PV) chez le rat hypophysectomisé. C.R. Acad. Sci. (Paris) 270, 385–388 (1970)
Kordon, C., Glowinski, J.: Role of hypothalamic monoaminergic neurones in the gonadotrophin-release regulating mechanisms. Neuropharmacology 11, 153–163 (1972)
Kraicer, J., Milligan, J.V.: Effect of colchicine on in vitro ACTH release induced by high K and by hypothalamus-stalk-median eminence extract. Endocrinology 88, 408–412 (1971)
Kreutzberg, G.W.: Neuronal dynamics and axonal flow. IV. Blockage of intra-axonal enzyme transport by colchicine. Proc. nat. Acad. Sci. (Wash.) 62, 722–728 (1969)
Lacy, P.E., Howell, S.L., Young, D.A., Fink, C.J.: New hypothesis of insulin secretion. Nature (Lond.) 219, 1177–1179 (1968)
La Vail, M.W., La Vail, J.H.: Retrograde intraaxonal transport of horseradish peroxidase in retinal ganglion cells of the chick. Brain Res. 85, 273–280 (1975)
LeBeux, Y.J., Willemot, J.: An ultrastructural study of the microfilaments in rat brain by means of heavy meromyosin labelling. I. The perikaryon, the dendrites and the the axon. Cell Tiss. Res. 160, 1–36 (1975)
Levêque, T.F., Stutinsky, F., Porte, A., Stoeckel, M.E.: Morphologie fine d'une différenciation glandulaire du recessus infundibulaire chez le rat. Z. Zellforsch. 69, 381–394 (1966)
Levêque, T.F., Stutinsky, F., Stoeckel, M.E., Porte, A.: Sur les caractéres ultrastructuraux d'une formation glandulaire périventriculaire dans l'éminence médiane du rat. C.R. Acad. Sci. (Paris) 260, 4621–4623 (1965)
McEwen, B.S., Grafstein, B.: Fast and slow components in axonal transport of protein. J. Cell Biol. 38, 494–508 (1968)
McLean, W.G., Keen, P.: Colchicine-binding activity and neurotubule integrity in a rat sympathetic ganglion. Exp. Cell Res. 80, 345–353 (1973)
MacLeod, R.M., Lehmeyer, J.E., Bruni, C.: Effect of antimitotic drugs on the in vitro secretory activity of mammotrophs and somatotrophs and on their microtubules. Proc. Soc. exp. Biol. (N.Y.) 144, 259–287 (1973)
Madarasz, B., Stoeckel, M.E., Hindelang-Gertner, C., Porte, A., Stutinsky, F.: Observations ultrastructurales sur les noyaux suprachiasmatiques de rats normaux, castrés et colchicinisés. C.R. Acad. Sci. (Paris) 278, 1253–1256 (1974)
Mahendran, M., Nichlas, W. J., Berl, S.: Evidence for calcium sensitive component in brain actomyosin-like protein (neurostenin). J. Neurochem. 23, 497–501 (1974)
Nauta, H.J.W., Kaiserman-Abramof, I.R., Lasek, R.J.: Electron microscopic observations of horseradish peroxidase transported from the caudoputamen to the substantia nigra in the rat. Possible involvement of the agranular reticulum. Brain Res. 85, 373–384 (1975)
Norström, A., Hansson, H.A.: Effects of colchicine on release of neurosecretory material from the posterior pituitary gland of the rat. Z. Zellforsch. 142, 443–464 (1973)
Norström, A., Hansson, H.A., Sjöstrand, J.: Effects of colchicine on axonal transport and ultrastructure of the hypothalamo-neurohypophyseal system of the rat. Z. Zellforsch. 113, 271–293 (1971)
Ochs, S.: Fast transport of materials in mammalian nerve fibers. A fast transport mechanism for materials exists in nerve fibers, which depends on oxidative metabolism. Science 176, 252–260 (1972)
Ochs, S.: Energy metabolism and supply of ∼P to the fast axoplasmic transport mechanism in nerve. Fed. Proc. 33, 1049–1058 (1974a)
Ochs, S.: Systems of material transport. Ann. N.Y. Acad. Sci. 228, 202–223 (1974b)
Otsuka, M., Otsuki, I., Ebashi, S.: ATP-dependent Ca-binding of brain microsomes. J. Biochem. (Tokyo) 58, 188–190 (1965)
Pecot-Dechavassine, M., Couteaux, R.: Modifications structurales des terminaisons motrices de muscles de grenouille soumis à l'action de la vinblastine. C.R. Acad. Sci. (Paris) 280, 1099–1101 (1975)
Peracchia, C.: A system of parallel septa in cray fish nerve fibers. J. Cell Biol. 44, 125–133 (1970)
Poisner, A.M., Bernstein, J.: A possible role of microtubules in catecholamine release from the adrenal medulla: effects of colchicine, vinca alkaloids and deuterium oxide. J. Pharmacol. exp. Ther. 177, 102–108 (1971)
Porte, A., Stoeckel, M.E., Brini, A.: Formation de l'ébauche oculaire et différenciation du cristallin chez l'embryon de poulet. Etude au microscope électronique. Arch. Ophtal. (Paris) 28, 681–706 (1968)
Puszkin, S., Berl, S., Puszkin, E., Clarke, D.D.: Actomyosin-like protein isolated from brain. Science 161, 170–171 (1968)
Repérant, J.: The orthograde transport of horseradish peroxidase in the visual system. Brain Res. 85, 307–312 (1975)
Rufener, C.: Autophagy of secretory granules in the rat neurohypophysis. Neuroendocrinology 13, 314–320 (1974)
Russel, J.T., Thorn, N.A.: Adenosine triphosphate dependent calcium uptake by subcellular fraction from bovine neurohypophyses. Acta physiol. scand. 93, 364–377 (1975)
Scherft, J.P., Heersche, J.N.M.: Accumulation of collagen containing vacuoles in osteoblasts after administration of colchicine. Cell Tiss. Res. 157, 353–365 (1975)
Schmitt, F.O.: The molecular biology of neuronal fibrous proteins. Neurosci. Res. Progr. Bull. 6, 119–144 (1968)
Seiden, D.: Effects of colchicine on myofilament arrangement and the lysosomal system in skeletal muscle. Z. Zellforsch. 144, 467–473 (1973)
Sjöstrand, J., Frizell, M., Hasselgren, P.O.: Effects of colchicine on axonal transport in peripheral nerves. J. Neurochem. 17, 1553–1570 (1970)
Sotelo, C., Riche, D.: The smooth endoplasmic reticulum and the retrograde and fast orthograde transport of horseradish peroxidase in the nigro striato nigral loop. Anat. Embryol. 146, 209–218 (1975)
Spooner, S., Yamada, K.M., Wessels, N.K.: Microfilaments and cell locomotion. J. Cell Biol. 49, 595–613 (1971)
Stoeckel, M.E., Dellmann, H.-D., Porte, A., Klein, M.J., Stutinsky, F.: Corticotrophic cells in the rostral zone of the pars intermedia and in the adjacent neurohypophysis of the rat and mouse. Z. Zellforsch. 136, 97–110 (1973)
Stoeckel, M.E., Hindelang-Gertner, C., Dellmann, H.-D., Porte, A., Stutinsky, F.: Subcellular localization of calcium in the mouse hypophysis. I. Calcium distribution in the adeno- and neuro-hypophysis under normal conditions. Cell Tiss. Res. 157, 307–322 (1975)
Stoeckel, M.E., Porte, A.: Observations ultrastructurales sur la parathyroide de souris. II. Etude expérimentale. Z. Zellforsch. 73, 503–520 (1966)
Stoeckel, M.E., Porte, A.: Observations ultrastructurales sur la parathyroide de mammifère et d'oiseau dans les conditions normales et expérimentales. Arch. Anat. micr. Morph. exp. pp55–87 (1973)
Stoeckel, M.E., Porte, A., Canguilhem, B.: Sur l'ultrastructure des cellules parafolliculaires de la thyroide du hamster sauvage. C.R. Acad. Sci. (Paris) 264, 2490–2492 (1967)
Stoeckel, M.E., Porte, A., Dellmann, H.-D., Gertner, C.: Selective staining of neurosecretory material in semithin epoxy sections by Gomori's aldehyde fuchsin. Stain Technol. 47, 81–85 (1972)
Sundberg, D.K., Krulich, L., Fawcett, C.P., Illner, P., McCann, S.M.: The effect of colchicine on the release of rat anterior pituitary hormones in vitro. Proc. Soc. exp. Biol. (N.Y.) 142, 1097–1100 (1973)
Thoa, N.B., Wooten, G.F., Axelrod, J., Kopin, I.J.: Inhibition of release of dopamine hydroxylase and norepinephrin from sympathetic nerves by colchicine, vinblastine or cytochalasin-B. Proc. nat. Acad. Sci. (Wash.) 69, 520–522 (1972)
Turner, P.R., Harris, A.B.: Ultrastructure of exogenous peroxidase in cerebral cortex. Brain Res. 74, 305–326(1974)
Twomey, S.L., Samson, F. Jr.: Tubulin antigenicity in brain particulates. Brain Res. 37, 101–108 (1972)
Wilson, L.: Microtubules as drug receptors: pharmacological properties of microtubule protein. Ann. N.Y. Acad. Sci. 253, 213–231 (1975)
Wunderlich, F., Müller, R., Speth, V.: Direct evidence for a colchicine-induced impairment in the mobility of membrane components. Science 182, 1136–1138 (1973)
Yamada, K.M., Spooner, B.S., Wessels, N.K.: Ultrastructure and function of growth cones and axons of cultured nerve cells. J. Cell Biol. 49, 614–635 (1971)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hindelang-Gertner, C., Stoeckel, ME., Porte, A. et al. Colchicine effects on neurosecretory neurons and other hypothalamic and hypophysial cells, with special reference to changes in the cytoplasmic membranes. Cell Tissue Res. 170, 17–41 (1976). https://doi.org/10.1007/BF00220108
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00220108