Summary
The effects of colchicine on ultrastructure of the lactating mammary cell in the rat and goat were studied by electron microscopy. Changes in tissue of the rat were examined over time (1, 2 and 4 h). The goat gland was evaluated by comparing ultrastructure of tissue at the time of maximum milk flow suppression induced by the drug with that of untreated tissue. Colchicine produced notable changes in the tissue of both species: 1) the secretion of lipid droplets and Golgi vesicle contents (exocytosis) was inhibited and the droplets and vesicles became randomly distributed throughout the cell, 2) the Golgi apparatus was significantly reduced in size, 3) casein and lipid continued to be synthesized as evidenced by greater numbers of secretory vesicles and increased sizes of casein micelles and lipid droplets, 4) secretory vesicles showed a propensity to cluster around lipid droplets, 5) isolated microtubules were found occasionally in the control tissue, ordinarily in the vicinity of the Golgi apparatus, but rarely in the colchicine-treated tissue. These observations indicate that colchicine has two effects leading to suppression of exocytosis in the mammary cell: one involves early interference with capacity of secretory vesicle membranes to fuse and a further effect, related to higher concentrations of colchicine, causes intracellular disorganization and loss of polarity. Microtubules were not seen as directly involved in the mechanisms of exocytosis. The secretion of milk fat globules is coupled to exocytosis and thereby is also inhibited by colchicine.
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Bargmann, W., Fleischhauer, K., Knoop, A.: Über die Morphologie der Milchsekretion II. Zugleich eine Kritik am Schema der Sekretionsmorphologie. Z. Zellforsch. 53, 545–568 (1961)
Bargmann, W., Welsch, U.: On the ultrastructure of the mammary gland. In: Lactogenesis: the initiation of milk secretion at parturition (M. Reynold and S.J. Folley, eds.). Philadelphia: University of Pennsylvania Press 1969
DeBrabander, M., Aerts, F., DeVeire, Van, R., Borgers, M.: Evidence against interconversion of microtubules and microfilaments. Nature 253, 119–120 (1975)
Franke, W.W., Lüder, M.R., Kartenbeck, J., Zerban, H., Keenan, R.W.: Involvement of vesicles coat material in casein secretion and surface regeneration. J. Cell Biol. 69, 173–195 (1976)
Guerin, M.A., Loizzi, R.F.: Effects of microtubule-altering drugs on lactose synthesis and secretion by lactating guinea pig mammary gland. Fed. Proc. 36, 343 (1977)
Herzog, V., Farquhar, M.G.: Luminal membrane retrieved after exocytosis reaches most Golgi cisternae in secretory cells. Proc. Natl. Acad. Sci. USA 74, 5073–5077 (1977)
Lacy, P.E., Howell, S.L., Young, D.A., Fink, C.J.: New hypothesis of insulin secretion. Nature 219, 1177–1179 (1968)
Lacy, P.E., Malaisse, W.J.: Microtubules and beta cell secretion. Recent Prog. Horm. Res. 29, 198–228 (1973)
Morré, D.J., Mollenhauer, H.H., Bracker, C.E.: Origin and continuity of Golgi-apparatus, pp. 82–126. In: Origin and continuity of cell organelles (J. Reinert and H. Ursprung, eds.). Berlin: Springer 1971
Moskalewski, S., Thyberg, J., Friberg, U.: In vitro influence of colchicine on the Golgi complex in A-and B-cells of guinea pig pancreatic islets. J. Ultrastruct. Res. 54, 304–317 (1976)
Nickerson, P.A.: Formation of concentric whorls of rough endoplasmic reticulum in the adrenal gland of the Mongolian gerbil. J. Anat. 124, 383–391 (1977)
Nicklas, W.J., Puszkin, S., Berl, S.: Effect of vinblastine and colchicine on uptake and release of putative transmitters by synaptosomes and on brain actomyosin-like protein. J. Neurochem. 20, 109–121 (1973)
Ollivier-Bousquet, M., Denamur, R.: Inhibition par la colchicine de la secretion des proteines du lait. C.R. Acad. Sci. [D] (Paris) 276, 2183–2186 (1973)
Orci, L., LeMarchand, Y., Singh, A., Assimacopaulos-Jeannet, F., Rouiller, C., Jeanrenaud, B.: Role of microtubules in lipoprotein secretion by the liver. Nature 244, 30–32 (1973)
Patton, S.: Reversible suppression of lactation by colchicine. FEBS Lett 48, 85–87 (1974)
Patton, S.: Mechanisms of secretion: Effects of colchicine and vinicristine on composition and flow of milk in the goat. J. Dairy Sci. 59, 1414–1419 (1976)
Patton, S.: Milk secretion at the cellular level: A unique approach to the mechanism of exocytosis. J. Dairy Sci. 61, 643–650 (1978)
Patton, S., Jensen, R.G.: Biomedical aspects of lactation, pp. 119. Oxford: Pergamon Press 1976
Patton, S., Stemberger, B.H., Knudson, C.M.: The suppression of milk fat globule secretion by colchicine: An effect coupled to inhibition of exocytosis. Biochim. Biophys. Acta 499, 404–410 (1977)
Patzelt, C., Brown, D., Jeanrenaud, B.: Inhibitory effect of colchicine on amylase secretion by rat parotid glands. J. Cell Biol. 73, 578–593 (1977)
Pipleers, D.G., Pipeleers-Marichial, M.A., Kipnis, D.M.: Microtubule assemply and the intracellular transport of secretory granules in pancreatic islets. Science 191, 88–90 (1976)
Pitelka, D.R., Kerkopf, P.R., Gagné, H.T., Smith, S., Abraham, S.: Characteristics of cells dissociated from mouse mammary glands. Exp. Cell Res. 57, 43–62 (1969)
Reaven, E.P.: Quantitative analysis of tubulin and microtubule compartments in isolated rat hepatocytes. J. Cell Biol. 75, 731–742 (1977)
Reaven, E.P., Reaven, G.M.: Distribution and content of microtubules in relation to the transport of lipid. J. Cell Biol. 75, 559–572 (1977)
Redman, C.M., Banerjee, D., Howell, K., Palade, G.E.: Colchicine inhibitors of plasma protein release from rat hepatocytes. J. Cell Biol. 66, 42–59 (1975)
Saacke, R.G., Heald, C.W.: Cytological aspects of milk formation and secretion, pp. 148–189, in Lactation, Vol. 2. New York and Lond: Academic Press 1974
Sandborn, E., Koen, P.F., McNabb, J.D., Moore, G.: Cytoplasmic microtubules in mammalian cells. J. Ultrastruct. Res. 11, 123–138 (1964)
Sherline, P., Leung, J.T., Kipnis, D.M.: Binding of colchicine to purified microtubule protein. J. Biol. Chem. 250, 5481–5486 (1975)
Spurr, A.R.: A low-viscosity epoxy resin embedding medium for electron microscopy. J. Ultrastruct. Res. 26, 31–43 (1969)
Stein, O., Stein, Y.: Colchicine-induced inhibition of very low density lipoprotein release by rat liver in vitro. Biochim. Biophys. Acta 306, 142–147 (1973)
Thyberg, J., Nilsson, S., Moskalewski, S., Hinek, A.: Effect of colchicine on the Golgi complex and lysosomal system of chondrocytes in monolayer culture. An electron microscopic study. Cytobiologie 15, 175–191 (1977)
Venable, J.H., Coggeshall, R.: Simplified lead citrate stain for use in electron microscopy. J. Cell Biol. 25, 407–408 (1965)
Warchol, J.B., Herbert, D.C., Rennels, E.G.: An improved fixation procedure for microtubules and microfilaments in cells of the anterior pituitary. Am. J. Anat. 141, 427–432 (1974)
Williams, J.A., Lee, M.: Microtubules and pancreatic amylase release by mouse pancreas in vitro. J. Cell Biol. 71, 795–806 (1976)
Wooding, F.B.P.: The mechanism of secretion of the milk fat globule. J. Cell Sci. 9, 805–821 (1971)
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Supported in part by grant HL 03622 of the U.S. Public Health Service
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Knudson, C.M., Stemberger, B.H. & Patton, S. Effects of colchicine on ultrastructure of the lactating mammary cell: Membrane involvement and stress on the Golgi apparatus. Cell Tissue Res. 195, 169–181 (1978). https://doi.org/10.1007/BF00233684
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DOI: https://doi.org/10.1007/BF00233684