The supression of milk fat globule secretion by colchicine: an effect coupled to inhibition of exocytosis

Patton, Stuart; Stemberger, Bridget H.; Knudson, Cynthia M.

doi:10.1016/0304-4165(77)90071-x

Cited by 49 publications

(8 citation statements)

References 16 publications

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“…milk [protein] increased), the concentration of fat was not significantly affected by colchicine treatment. In the latter respect our results differ from those of Patton, Stemberger and Knudson [1977] who found an increase in [fat] after 36-48 h in goats treated in the same way.…”

Section: Discussioncontrasting

confidence: 99%

The Effects of Colchicine on Milk Secretion, Mammary Metabolism and Blood Flow in the Goat

Henderson

Peaker

1980

Exp Physiol

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Mammary function in the consciouLs gloat was stLidied during colchicine-induced depression of milk secretion in one mammar gland. Milk yield of the treated gland WaS reduced to approximately a quarter of previous, w-hile there were significant increases in afternoon milk yield from the untreated glands on the 2nd and 3rd days after treatment in goats in late lactation. Milk composition in the untreated glands was not significantly affected. In the treated gland, milk [Na'j, [Cl-] Mammary.extractions ((A-V) A) of glucose, acetate and most amino acids were significantly decreased during the period of maximal inlibition of secretion. There were no significant changes in arterial plasma concentrations of glucose, acetate or any essential amino acids. In another series of experiments, mammary blood flow increased and then returned to normal after colchicine treatment even though milk yield and mammary glucose uptake decreased markedly; oxygen uptake was not significantly affected.The results are discussed in relation to the actions of colchicine on the mammary secretory cell, to the normal control of mammary blood flow and to the mechanism of compensation by the untreated gland.The plant alkaloid, colchicine, and its derivatives, have been shown to interfere with secretory processes in a number of tissues; for example, insulin secretion from the pancreas [Lacy, Howell, Young and Fink, 1968], neuro-transmitter release from synaptosomes [Nicklas, Puszkin and Berl, 1973] and release of catecholamines from the adrenal medulla [Poisner and Bernstein, 1971] are all inhibited by colchicine. These effects are thought to occur as a result of the binding of colchicine to microtubules and the consequent disturbance of intracellular transport and exocytosis of the secretory product.The effects of colchicine on the secretion of a complex mixture, namely milk, are of particular interest. Patton [1974] demonstrated that colchicine temporarily inhibits milk secretion when injected into the lumen of the mammary gland in goats. Subsequent work in vitro [Patton, 1978;Guerin and Loizzi, 1978] has suggested that the rate of secretion of all the major constituents of milk is decreased. However, the questions remain of whether synthesis of milk components as well as secretion, is inhibited, and of whether the ionic composition of milk is affected. Therefore, we have examined the effects of colchicine on mammary substrate tiptake and blood flow, and on the composition of the atqueous phase of milk. It will be seen that the effects of 367

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Section: Discussioncontrasting

confidence: 99%

The Effects of Colchicine on Milk Secretion, Mammary Metabolism and Blood Flow in the Goat

Henderson

Peaker

1980

Exp Physiol

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“…Most were oriented perpendicular to the apical plasma membrane and concentrated in the apical and medial portions of the cell cytoplasm [8]. These microtubules were found in close contact with secretory vesicles, and treatment with colchicine was found to inhibit exocytosis as well as to suppress milk fat globule secretion [9,10]. Specific molecules involved in the interaction between the cytoskeleton and secretory vesicles and CLDs remain unknown, and although CLDs are covered by a protein coat, the protein composition is largely undefined.…”

Section: Introductionmentioning

confidence: 99%

Proteomics reveal a link between the endoplasmic reticulum and lipid secretory mechanisms in mammary epithelial cells

Wu¹,

Howell²,

Neville

et al. 2000

Electrophoresis

198

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The synthesis and secretion of lipids by mammary epithelial cells is a highly ordered process that involves several distinct steps. Triacylglycerols are synthesized in the endoplasmic reticulum and incorporated into microlipid droplets which coalesce into cytoplasmic lipid droplets. These are vectorially transported to the apical plasma membrane where they are secreted into the milk surrounded by a membrane bilayer. The origin of this membrane as well as the mechanism by which cytoplasmic lipid droplets form and become surrounded by membrane is poorly understood. Proteomic analysis of the protein composition of milk fat globules and cytoplasmic lipid droplet has revealed that the endoplasmic reticulum is not only involved in the synthesis of the lipid but also potentially contributes to the membrane component of milk fat globules. The proteins identified suggest possible mechanisms of multiple steps during this process. Completion of the proteome of milk fat globule membranes and cytoplasmic lipid droplets will provide the necessary reporter molecules to follow and dissect the mechanisms of the sorting and ultimate secretion of cytoplasmic lipid droplets.

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“…D EPOLYMERIZATION of microtubules in lactating mammary gland by colchicine and related drugs interferes with milk flow (1) and the secretion of several milk components including protein (2)(3)(4), fat (2,3), and lactose (5,6). Microtubules may facilitate secretion at several sites, including transport of newly formed proteins from the endoplasmic reticulum to the Golgi complex and exocytosis of secretory granules into the lumen (4,7).…”

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confidence: 99%

Progesterone Withdrawal Stimulates Mammary Gland Tubulin Polymerization in Pregnant Rats*

Loizzi¹

1985

Endocrinology

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The size of the polymerized tubulin pool in mammary glands of late pregnant rats increased 2.4-fold 24 h after bilateral ovariectomy using a [3H]colchicine binding assay for tubulin. The total (free plus polymerized) tubulin concentration was not altered. Stimulation of tubulin polymerization as well as the induced rise in lactose content were both completely inhibited in rats that had been fitted with progesterone implants at the time of surgery. The increase in polymerized tubulin was not blocked by 17 beta-estradiol implants, although this treatment did partially inhibit the rise in tissue lactose following ovariectomy. The results indicate that increased polymerization during induced lactogenesis reflects a shift of free tubulin into the polymerized pool and that this shift is related to the withdrawal of progesterone.

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The supression of milk fat globule secretion by colchicine: an effect coupled to inhibition of exocytosis

Cited by 49 publications

References 16 publications

The Effects of Colchicine on Milk Secretion, Mammary Metabolism and Blood Flow in the Goat

The Effects of Colchicine on Milk Secretion, Mammary Metabolism and Blood Flow in the Goat

Proteomics reveal a link between the endoplasmic reticulum and lipid secretory mechanisms in mammary epithelial cells

Progesterone Withdrawal Stimulates Mammary Gland Tubulin Polymerization in Pregnant Rats*

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