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

Abstract

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

Arterial Plasma Composition During Compensatory Increase in Milk Secretion in the Goat: Relation to Rate Limitation

“…As shown previously (Henderson & Peaker, 1980, 1983, colchicine treatment caused a marked temporary reduction in milk secretion in the treated gland; yield fell to 60% of the previous level 24 h after the first injection and to 40% after 48 h. Meanwhile there was a compensatory increase in the untreated gland, reaching a peak of 126% of the previous level at 48 h. Values for yield in ml/h are given in Table 1. Arterial plasma composition On the first day after start of treatment, the concentrations of lysine (71 % of the previous level) and arginine (78 %) (of the 'essential' amino acids), glycine (71 %), alanine (73 %) and ornithine (58%) ('non-essential' amino acids) were significantly decreased, whereas that of glucose (1160%) was significantly increased (Table 1).…”

“…During the period of decrease in substrate demand by the treated gland (Henderson & Peaker, 1980) and the compensatory increase in the other, a rise in arterial concentration of one or more substrates could indicate that before treatment these substrates were directly limiting milk secretion at the mammary level at peak lactation. Accordingly arterial substrate concentrations were determined twice daily for 1 d before, and 3 d after, treatment.…”

“…Although tyrosine is one of the amimo acids in which uptake from plasma is virtually equal to output into milk protein (see Mepham, 1976) its extraction (extraction = arteriovenous concentration difference as a percentage of arterial concentration) by the mammary gland is relatively low (45O%, Mepham & Linzell, 1966; 360%, Henderson & Peaker, 1980) and it is unlikely that an increase in tyrosine supply could permit an increase in milk secretion. There was no evidence for direct substrate limitation by the essential amino acids which have a high mammary extraction, which are transferred quantitatively to milk, and which are generally considered as candidates for rate limitation (methionine and phenylalanine).…”

“…Henderson & Peaker (1980) found that when secretion in one mammary gland of goats in late lactation was chemically inhibited, the rate of milk secretion in the other gland increased. During the compensatory increase there were no significant effects on the concentrations of key substrates for milk secretion in arterial plasma, a finding inconsistent with direct substrate limitation on milk secretion.…”

“…They showed that direct substrate limitation did not take place at either (i) ascending lactation or (iii) declining lactation. Their work, taken along with that of Henderson & Peaker (1980), showed that direct substrate limitation only remained a possibility at peak lactation.…”