Effects of colchicine on ultrastructure of the lactating mammary cell: Membrane involvement and stress on the Golgi apparatus

Abstract

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.

Influence of Colchicine on Lactating Mammary Gland of the Cow and Rat with Special Reference to the Exocytosis and to the Milk Fat Globule Secretion

“…KNUDSON et al (1978) have reported a similar finding in the goat mammary gland infused with colchicine. Moreover, when the milk secretion is supressed, an increase in the number of microvilli was observed.…”

“…Microtubules have been observed in cow and rat lactating mammary cells (BOMMELI, 1972;MORALES, 1977MORALES, /1979KNUDSON et al, 1978). However, after treatment with colchicine they can not be observed in the cytoplasm of the secreting cells.…”

Differentiation of epidermal cells in the regenerating planarian Dugesia japonica

“…Inasmuch as cytochalasin B had little effect on the polarized distribution of organelles in epidermal cells, however, it appears that actin is not involved in the motility establishing cell polarity. A complex of lo-nm filaments (intermediate filaments) plus microtubules appears to play a role in distribution of cytoplasmic components in various other epithelial cells (Knudson et al, 1978;Wang & Goldman, 1978;Simons & Fuller, 1985), apparently providing tracks for intracellular movement. In planarian epidermal cells, intermediate filaments are preferentially localized toward the base of the cell (Hori, 1989), not in a position where they would directly affect the intracellular movements necessary to establish the polarized localization of organelles.…”

The Effects of Vincristine on Milk Secretion and Milk Composition in the Goat

“…Indeed, recent work shows that anti-microtubule agents reduce the activity of other glycosyltransferases (Mitranic, Boggs & Moscarello, 1981;Azhar et al 1983). Ultrastructural evidence also shows disruption of the Golgi apparatus, the site of lactose synthesis, by colchicine (Knudson, Stemberger & Patton, 1978) and vinblastine (Nickerson, Smith & Keenan, 1980) while autoradiographic evidence, demonstrating preferential binding of colchicine to Golgi and plasma membranes (Houdebine et al 1982) also suggests the Golgi as a site of action for the drug. This proposal, of a specific action of vincristine on lactose synthesis in the Golgi apparatus, may equally be made for the effects of colchicine on milk secretion since during colchicine inhibition the secretion of lactose and protein are also affected to different degrees (Henderson & Peaker, 1980); biochemical evidence also supports the idea of an effect on lactose synthesis by colchicine (Faulkner, Henderson & Peaker, 1985).…”