Mammary cell proliferation in mice during pregnancy and lactation in relation to milk yield.
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Animals↗
Biomedical subjects
M Peaker
Publications and source records attributed to M Peaker.
Effects of frequent milking on milk secretion during lactation in the goat: relation to factors which limit the rate of secretion.
Goats were milked hourly with the aid of oxytocin at different stages of lactation. Udder volume and milk yield were also measured. The marked variation between goats in the time after parturition at which peak milk yield is attained and in the rate of decline after peak is illustrated. Hourly milking had a stimulatory effect on the rate of milk secretion in early lactation (before peak) and in declining lactation (after peak), in both cases at previous milk yields of 1.1 - 1.48 g/ml udder volume . d. There was no stimulatory effect of hourly milking on milk yield at or near peak lactation (yield before the experiment greater than 1.48 g/ml volume . d) or in late lactation (less than 1.1 g/ml . d). The responses of milk yield to hourly milking are discussed in relation to the factors which limit the rate of secretion. In particular, it is concluded that a stimulatory response indicates that before the experiment the rate of secretion could not have been limited directly by the arterial supply of one or more substrates for milk synthesis. It is stressed that the results were obtained under one dietary regime only.
Animals↗
Calcium fluxes in mouse mammary tissue in vitro: intracellular and extracellular calcium pools.
1. The total Ca content of the mammary gland increased from about 2 to 12 mumole/g tissue during the transition from pregnancy to lactation in the mouse. In tissue from lactating mice at least two thirds of the total Ca exchanged with external Ca in 6 hr. There was little non-exchangeable Ca in tissues from pregnant mice.2. At 37 degrees C the time courses of influx and efflux of (45)Ca in lactating tissues could be analysed by assuming three exponential components with rate constants of about 0.3, 0.06 and 0.005 min(-1) and containing, respectively, 1.7, 1.5 and 4.7 mumole (45)Ca/g tissue at the steady state.3. The rapidly effluxing component showed the time- and temperature-dependence characteristic of bulk-phase-limited diffusion through the extracellular space. The diffusion coefficient was about one quarter of the self-diffusion coefficient of Ca in aqueous solution, consistent with a tortuosity factor of about 2. A portion of the Ca in this component was displaced by La(3+). The amount remaining in the presence of 3 mm-La(3+) was close to that expected for free extracellular Ca. The rapid component was therefore interpreted as originating from an extracellular compartment containing both free and bound Ca.4. The rate of efflux of the intermediate component was slowed by a factor of ten when the temperature was decreased from 37 to 0 degrees C giving a Q(10) of 2.7, expected for membrane transport. The slow component present at 37 degrees C was not displaced by EGTA or La(3+), suggesting that it is not localized extracellularly. It was not apparent in the 0 degrees C efflux curves.5. The biphasic time course of uptake of ionophore (A23187)-releasable (45)Ca in particulate fractions obtained by homogenization and centrifugation of tissues which had been incubated with the isotope was consistent with the hypothesis that the two slower components of (45)Ca flux originate from intracellular compartments. Mitochondrial uptake probably did not contribute significantly to Ca exchange in these tissues.6. (45)Calcium fluxes in mammary tissues from pregnant mice also showed three components with rate constants similar to those found in tissues from lactating mice. The amount of Ca in each component was much smaller than in lactating tissue when compared on the basis of tissue weight.7. We conclude from these studies that: (i) intra- and extracellular Ca pools in mammary tissue can be distinguished on the basis of the temperature dependence of their fluxes and (ii) the transition from pregnancy to lactation is accompanied by large increases in both intra- and extracellular Ca pools in mammary alveolar cells.
Animals↗
Mammary development in mice: effects of hemihysterectomy in pregnancy and of litter size post partum.
1. Mice were hemihysterectomized on day 8 of pregnancy to reduce the number of feto-placental units.2. Fetal mortality was not affected by hemihysterectomy; mean single-pup weight at birth was increased when compared with sham-operated controls.3. Pregnant sham-operated and hemihysterectomized animals were killed on days 13 and 18 of gestation, and their mammary glands were analysed for total DNA (DNA(t)) and RNA (RNA(t)). Both were significantly lower in the hemihysterectomized group on day 18, but not on day 13.4 Milk yield was assessed, by daily weighing of the litter, in groups of sham-operated and hemihysterectomized lactating animals suckling nine pups each. There was no difference in yield between the two groups.5. One group of sham-operated mice suckling nine pups, one of hemihysterectomized mice suckling nine pups and one of hemihysterectomized mice suckling four pups were killed on day 5 of lactation for mammary gland analysis. There was no significant difference in mammary weight or DNA(t) between the sham-operated and hemihysterectomized animals suckling nine pups, although RNA(t) was still reduced in the latter. Mammary weight, DNA(t) and RNA(t) were all significantly lower in the hemihysterectomized group suckling four pups than in either of the other two groups.6. It is concluded that the less well developed mammary glands of mice which give birth to small litters are capable of compensatory growth during the first few days of lactation if a sufficiently strong suckling stimulus is given.7. It is suggested that control of mammary development by the fetus during gestation and by the suckling young during early lactation are both mechanisms designed to ensure that milk yield is appropriate to the needs of the young.
Animals↗
Development of the mammary gland.
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Adrenal Cortex Hormones↗
Metabolic significance of milk glucose.
The free glucose concentration in the aqueous phase of samples of goat, sheep, cow, rat and rabbit milk was about 0.1-0.3 mM, while that in human milk was about 2mM. During starvation the glucose concentration of goat milk fell considerably (by about 80% in 2 d) in parallel with the decreased rate of lactose production. With rats fed ad lib., glucose concentration in the milk was greater at 12.00 h than at 18.00 h, when lactose synthesis has been shown to decrease. 3-O-Methyl-D-glucose injected into the goat mammary gland via the teat canal specifically entered the blood. These findings support the idea that glucose equilibrates across the apical membrane of mammary secretory cells, so that milk concentrations reflect intracellular glucose concentratioins.
Animals↗
Changes in milk citrate concentration during lactation in the goat.
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Animals↗
Changes in the concentrations of the minor constituents of goat's milk during starvation and on refeeding of the lactating animal and their relationship to mammary gland metabolism.
1. Changes in the concentrations of the minor constituents of goat's milk were observed during 48 h starvation and on refeeding. 2. The concentrations of hexose phosphate and UDP-hexoses increased during starvation and decreased on refeeding. 3. The concentrations of phosphoenolpyruvate and glycerate 3-phosphate decreased during starvation and increased on refeeding. 4. Isocitrate:2-oxoglutarate increased during starvation and decreased on refeeding. 5. Changes in the minor constituents of milk can be explained in terms of the metabolic changes occurring in the mammary gland during starvation. It is proposed that changes in the concentrations of these metabolites in milk reflect changes in their concentrations in the cytosol or Golgi vesicles of the mammary gland.
Animals↗
Ionized calcium in milk and the integrity of the mammary epithelium in the goat.
1. Injection of citrate or EGTA solutions into the lumen of the mammary gland of goats in quantities sufficient to reduce ionized calcium to less than one-tenth of normal, led to increases in milk concentrations of Na and Cl and decreases in K and lactose. 2. Subsequent milk yields were decreased in glands treated with citrate but not in those treated with EGTA. 3. Blood-milk potential difference decreased (i.e. towards zero) in glands in which citrate was present. 4. In goats milked hourly with the aid of oxytocin, milk Na and Cl concentrations increased while K and lactose decreased; there was no apparent decrease in Ca2+ concentration. 5. It is suggested that ionized calcium in milk is essential to preserve the integrity of the mammary epithelium during lactation.
Animals↗
Milk composition in the plains viscacha (Lagostomus maximus).
Milk samples were taken from 10 plains viscacha between 9 and 64 days post partum. Mean concentrations (+/- s.e.) were 17 +/- 1.1 mM-Na; 32 +/- 1.6 mM-K; 35 +/- 2.2 mM-Cl; 116 +/- 3.3 mM-lactose (total reducing sugar) (all in 8 samples); less than 10-220 mg citrate/l (range of 4 samples); 15.7 +/- 0.64 g total nitrogen/l (3 samples). The Na:K ratio was 1:1.95 +/- 0.17. It was estimated that the fat concentration was between 116 and 182 g/l.
Animals↗
Mastectomy and mammary glands in reproductive control in the goat.
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Animals↗
The utilization of glucose for the synthesis of milk components in the fed and starved lactating goat in vivo.
1. [U-14C]Glucose and [3-3H]glucose were infused into fed and starved lactating goats in order to study glucose metabolism in the mammary gland. 2. Glucose carbon was oxidized and metabolizet to milk lactose, citrate and triacylglycerol in the lactating goat udder. 3. Recycling of glucose carbon in the lactating animal accounted for 10-20% of the total glucose turnover in the whole animal. Recycling of glucose 6-phosphate in the udder accounted for about 25% of the glucose 6-phosphate metabolized. 4. Flux of glucose 6-phosphate through the pentose phosphate pathway was sufficient to account for 34% of the NADPH required for fatty acid synthesis in the gland in the fed animal. 5. Net metabolism of glucose 6-phosphate via the pentose phosphate pathway accounted for 17.8 and 1.2% of the glucose phosphorylated by the mammary gland in the fed and starved animal respectively. Metabolism of glucose 6-phosphate via the pentose phosphate pathway was sufficient to account for all the CO2 produced from glucose in the fed animal, but only 17% of the CO2 produced from glucose in the starved animal.
Animals↗
Effects of starvation on cardiovascular function (including the mammary circulation) and water balance in pregnant goats.
In conscious goats, starved for 48 hr, in mid-pregnancy (70 days) cardiac output and blood volume decreased; total peripheral resistance increased; heart rate, stroke volume, blood pressure, mammary blood flow and mammary resistance were not significantly affected. In late pregnancy (132 days) cardiac output, heart rate, blood volume and mammary blood flow fell; peripheral resistance increased; stroke volume and blood pressure were not significantly affected. In mid-pregnancy, water consumption fell and the animal entered a stage of negative sensible water balance which persisted for both days of starvation. A similar change was obtained on the first day in late-pregnant goats, but on the second day water consumption increased and positive water balance was restored. Cardiac output, heart rate, blood volume and mammary blood flow was higher in fed late-pregnant than in fed mid-pregnant goats, total peripheral resistance was lower while there were no significant changes in stroke volume or blood pressure. Indications of correlations between litter size and cardiac function were obtained. The results are compared with previous studies on the effects of starvation in lactating animals and are discussed in relation to the control of cardiac function and mammary blood flow in pregnancy and lactation.
Animals↗
The effects of colchicine on milk secretion, mammary metabolism and blood flow in the goat.
Mammary function in the conscious goat was studied during colchicine-induced depression of milk secretion in one mammary gland. Milk yield of the treated gland was reduced to approximately a quarter of previous, while 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+], [Cl-], [citrate] and [protein] increased while [K+] and [lactose] decreased, although the time course of these changes differed; milk [fat] was unaffected. Mammary extractions ((A-V)/A) of glucose, acetate and most amino acids were significantly decreased during the period of maximal inhibition 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.
Animals↗
The effect of raised intramammary pressure on mammary function in the goat in relation to the cessation of lactation.
1. The effects of raising intramammary pressure on mammary function have been studied in conscious goats. 2. When intramammary pressure was raised to levels which normally occur following cessation of milking (by infusing isosmotic sucrose into the lumen of the gland) the rate of milk secretion fell within 6 hr, but in short-term studies at these pressures, there was no reduction in mammary blood flow (in fact there was a significant increase) and no change in oxygen consumption or glucose uptake. 3. At pressures more than twofold higher than those which occur under physiological conditions, there was a decrease in mammary blood flow within 5 min; in addition the arterio-venous difference for oxygen, but not for glucose, fell. The changes were reversed when pressure was lowered. Similar results were obtained in autotransplanted (denervated) glands. 4. Intramammary pressure-volume curves were determined 3 days before cessation of milking. By determining the rate of secretion after cessation it was evident that the rate of secretion fell as the pressure-volume curve steepened. 5. A positive correlation was found between empty gland volume and functional capacity of the gland (volume of liquid needed to raise intramammary pressure to 30 mmHg at the tip of the teat) in goats of the Saanen breed. 6. No apparent effect on blood-milk potential difference was obtained at pressures within the range observed after cessation of milking. At higher pressures, the potential difference fell, eventually to zero. 7. It is concluded that in the goat the arrest of milk secretion following cessation of milking is caused by mammary distension but is not due to a primary effect of mammary distension on blood flow, and that the loss of integrity of the mammary epithelium, which also occurs, is not due simply to mechanical rupture. 8. From present and previous studies, a scheme is proposed to account for the control of mammary function after the cessation of milking in late lactation in the goat.
Animals↗
Local production of prostaglandins in relation to mammary function at the onset of lactation in the goat.
1. Arterial and mammary venous concentrations of prostaglandins F alpha (PGF alpha), E (PGE) and the PGF alpha metabolite, 13,14-dihydro-15-oxoPGF alpha (DHK-PGF alpha) were studied during late pregnancy and the onset of lactation in conscious goats. Mammary secretion concentrations of PGF alpha and DHK-PGF alpha were determined, and mammary blood flow, arterial plasma progesterone concentrations and milk composition were also studied. 2. A significant output of PGF alpha from the mammary gland into mammary venous blood was observed during late pregnancy; this output ceased near term. 3. Mammary output of DHK-PGF alpha into venous blood began about 6 days prepartum, suggesting an increasing capacity of the gland to metabolize PGF alpha. 4. The concentration of PGF alpha in mammary secretion increased from about 4 days pre-partum, that of DKH-PGF alpha from about 12 days pre-partum. 5. It is concluded that although total mammary output of PGF alpha decreases during late pregnancy and early lactation, the rate of mammary synthesis of PGF alpha increases and the PGF alpha is increasingly secreted into milk and metabolized to DHK-PGF alpha within the mammary gland. 6. Unilateral treatment of one mammary gland in goats with the PGF 2 alpha analogue, Cloprostenol, at two dose levels from 2-3 days pre-partum to 1-2 days post-partum prevented the changes in milk [Na] that occur at term in untreated glands. At the higher dose, the normal rise in milk [citrate] was abolished and milk yield was reduced; these effects persisted after cessation of treatment. 7. It is suggested that PGF alpha may play a local inhibitory role in mammary gland function during late pregnancy. It is further suggested that PGF alpha could be the factor, or one of the factors, proposed by Linzell & Peaker (1974) to be responsible for local control of mammary epithelial permeability and possibly also for secretory rate.
Animals↗
Effects of starvation on the cardiovascular system, water balance and milk secretion in lactating goats.
During starvation in the lactating goat, cardiac output, stroke volume, mammary blood flow, blood volume and the rate of milk secretion decreased markedly; total peripheral resistance and haematocrit increased while arterial blood pressure and plasma osmolality remained unchanged. Water consumption decreased markedly and the animals went into negative water balance even though water was available throughout.
Animals↗