BIOCHEMICAL ASPECTS OF MAMMARY GLAND FUNCTION

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Abstract
Summary: 1. The arterio‐venous technique, hitherto favoured for mammary gland studies, is subject to drawbacks which make it unsuitable for quantitative work, as many conflicting results attest. This technique in its present form is capable of yielding only the broadest qualitative conclusions. It is claimed that one source of uncertainty is minimized by the use of anaesthetized animals. Studies on the isolated perfused udder and surviving tissue slices have given useful results; tracer isotopes, so far hardly used in this field, may solve many outstanding problems.2. Mammary slices respire fairly actively compared with other tissues. In the rat there is a marked increase in respiration at parturition, correlated with hormonally controlled changes in mammary gland metabolism, and the respiration further increases with increasing milk yield. Glucose and mannose are the only sugars so far found which increase the oxygen uptake of rat mammary gland slices above endogenous values.3. Studies in vivo and in vitro alike indicate a high respiratory quotient for the lactating gland which may mean the synthesis of fat from oxygen‐rich precursors. Studies in vitro suggest that in the non‐ruminant the fat precursor may be carbohydrate while the ruminant gland probably synthesizes fat from acetate. Non‐lactating gland gives an R.Q. less than unity and the hormonally controlled events associated with parturition are accompanied by a rapid increase in the R.Q. to values greater than unity.4. The source of energy of the active gland is not yet clear; there is evidence that carbohydrate, long‐chain fatty acids, β‐hydroxybutyric acid and acetate can be oxidized.5. Mammary gland slices show appreciable anaerobic glycolysis (acid production) which is decreased in presence of oxygen. It is possible that part of the aerobic acid production may be due to formation of citric acid or fatty acids.6. Enzymes recently detected in mammary tissue comprise desoxyribonuclease, catalase, xanthine dehydrogenase, and acid phosphatase. Most attention has been given to the alkaline phosphatase and arginase, both of which occur abundantly in lactating gland in certain species.The concentration of alkaline phosphatase in the rat mammary gland increases rapidly during late pregnancy to a constant high level which is maintained throughout lactation, indicating that the enzyme is concerned with mammary function rather than growth. Histoenzymatic studies have suggested that this enzyme is mainly localized in the myoepithelium and capillary endothelium, there playing a role associated with transport of metabolites, rather than in the secretory epithelium, but this needs further confirmation.Changes in the arginase levels of the mamma in the rat during lactation suggest that deamination processes probably associated with gluconeogenesis from protein or amino‐acids play an important role in mammary metabolism in this species. The arginase content of the mamma is low in herbivores (including ruminants) so that deamination in the mammary gland must be less prominent in these forms.7. Present evidence indicates that glucose is the principal blood precursor of lactose, though other hexoses, absorbed from the blood as glycoprotein, may supplement the carbohydrate supplies of the udder. There is no evidence for the absorption of blood lactate and pyruvate by the mammary gland.The role of glycogen, present in disputed amounts in mammary tissue, in lactose formation, is not clear; it may be an obligatory intermediate or merely a reserve of carbohydrate. Mammary glycogen levels can be experimentally increased by perfusion of the isolated gland with hyperglycaemic blood, particularly in presence of insulin, or by weaning.The mode of formation of the galactose moiety of the lactose molecule is still obscure. There is no evidence that galactose transported to the mamma in the blood is necessary for lactose synthesis, and its formation in the free state from glucose in the gland, prior to condensation with glucose to give lactose, is contra‐indicated by the available evidence. The possibility that glucose is transformed enzymatically to a galactose phosphate before condensation is considered and a tentative scheme of biological lactose synthesis on this basis is proposed.8. Part of the milk fat undoubtedly arises from neutral blood fat, probably from the glyceride fraction, but the high R.Q. of the lactating gland indicates that some at least of the fat may be synthesized from oxygen‐rich compounds. The facts that cow and goat udder slices apparently do not utilize glucose with high R.Q. as tissues from other species do, but unlike other species utilize acetate with high R.Q., suggest the possibility that the ruminant udder may synthesize fat from acetate. If so it seems likely that the short‐chain acids of ruminant milk may arise in this way, rather than from carbohydrate or by partial oxidation of long‐chain fatty acids as previously suggested.9. Very little is known about the mode of synthesis of milk protein. The amount of free amino‐acids absorbed from the blood by the udder is too small to account for the milk protein and it is probable that some fraction of the blood proteins is transformed into the proteins of milk.10. It appears that the mammary gland, like the liver, can deaminate amino‐acids with the production of urea–at least in some animals, and it is likely that in forms in which the mammary gland arginase levels are elevated during lactation, the process is an important element in the metabolism of the lactating gland. In such forms the partial inhibition of lactation following adrenalectomy may be due to depression of gluconeogenesis from protein in the mammary gland. A curious anomaly is the low concentration of arginase in the udder of the goat, the only animal in which direct evidence of urea production by the mammary gland has yet been obtained.11. In the rat and probably other animals lactation demands an increase in the liver arginase level above that of pregnancy, probably indicative of increased gluconeogenesis from protein to meet the requirements of the mammary gland for carbohydrate.