Milk Release Research Articles

Naloxone cannot abolish the lack of oxytocin release during unexperienced suckling of dairy cows

To evaluate the role of opioids for the regulation of oxytocin release in response to teat stimulation, 10 brown-Swiss dairy cows were randomized to two experiments during mid of lactation. In the first experiment, four cows without previous suckling experience were suckled by an alien calf between two normal milkings. Before and during milking or suckling, frequent blood samples were collected via a jugular cannula for determination of oxytocin and β-endorphin. In the second experiment, six cows were treated with naloxone or saline, 10 min before the start of the first or second suckling, respectively. The collected blood samples were assayed for oxytocin. In the first experiment, the plasma levels of β-endorphin were elevated during and after the unexperienced suckling in three cows, but not in the fourth cow, and the release of oxytocin during suckling was markedly reduced, suggesting no release of alveolar milk. In the second experiment, the release of oxytocin during suckling was again significantly reduced. Pretreatment with naloxone before suckling did not completely abolish the adverse effect of suckling and the oxytocin plasma level did not increase to levels comparable with control milking. In emotional stress situations, the release of oxytocin from the pituitary is inhibited with simultaneously elevated β-endorphin plasma levels. Although there is some evidence for a regulatory role of opioids for the release of oxytocin, other mediators are suggested to be more potent in regulating oxytocin under stress conditions.

Mammary-derived signals activate programmed cell death during the first stage of mammary gland involution.

Programmed cell death (PCD) of mammary alveolar cells during involution commences within hours of the end of suckling. Locally, milk accumulates within alveolar lumens; systemically, levels of lactogenic hormones fall. Four experimental models were used to define the role of local factors as compared with systemic hormones during the first and second stages of involution. In three models, milk release was disrupted in the presence of systemic lactogenic hormones: (i) sealing of the teats, (ii) mammary gland transplants that cannot release milk due to the absence of a teat connection, and (iii) inactivation of the oxytocin gene. The ability of systemic hormones to preserve lobular-alveolar structure without blocking PCD was illustrated using a fourth transgenic model of lactation failure. During the first stage of involution, local signals were sufficient to induce alveolar PCD even in the presence of systemic lactogenic hormones. PCD coincided with bax induction, decreased expression of milk proteins, block of prolactin signal transduction through Stat5a and 5b, and activation of Stat3. The two stages of mammary gland involution are regulated by progressive gain of death signals and loss of survival factors. This study demonstrates that genetic events that occur during the first reversible stage are controlled by local factors. These mammary-derived death signals are dominant over protective effects related to systemic hormone stimulation.

Udder massage after milk release in pigs: does it keep milk production steady and equally allocated?

Piglets usually massage teats after milk let-down, but the function of this final massage (FM) is not clear. Five hypotheses were formulated: (A) FM helps to smooth nursing-to-nursing fluctuations in milk production; (B) FM enables left-behind piglets to signal their needs and enhance milk intake; (C) larger piglets use FM to increase their milk consumption; (D) slowly growing litters massage more, increasing thereby their mothers’ milk production; (E) strong litters massage more, perpetuating superior milk production in their mothers. We recorded FM duration, FM intensity (number of massaging movements per second) and milk transfer (weigh-suckle-weigh method) in 12 litters for 6 h day-’ on days l-3 post-partum. On day 3, hypothesis (A) was supported: there was a withinpiglet negative correlation between the piglet’s FM intensity on a nursing and its weight gain during the preceding two nursings ( r= 0.3 1, P < 0.001) and there was a within-teat correlation between the teat’s output on a nursing and mean FM intensity received during the preceding two nursings (r=0.28, P <O.OS)‘. Over the third day, the sow’s milk output on a nursing (relative to her daily mean) depended on litter FM duration during the last two nursings (r= 0.47, P < 0.001). Hypotheses (B) and (D) were partly supported in that piglets which gained less weight (relative to litter mean) between days 1 and 3 massaged more intensely on day 3 (r= -0.23, P<O.O5), and litters which grew less between days 1 and 3 massaged longer on day 3 (r= 0.78, P <O.OOl). In conclusion, by day 3, FM seems to dampen milk output fluctuations and soften milk income differences within and between litters.

Effects of diabetes mellitus on lactation in the rat.

Diabetes mellitus adversely affects the process of lactation. Although insulin administration restores lactation, the manner by which it does so is unknown. The goals of this study were to determine which phase of lactation, milk synthesis/supply (MS), and/or milk release (MR) was affected. Inasmuch as insulin, corticosterone, and prolactin, among other hormones, are involved in milk synthesis in vitro, this study investigated their probable roles in the suppression of lactation in diabetes in vivo. Diabetes was induced in rats on Day 3 postpartum with streptozotocin (50-60 mg/kg, ip). Milk synthesis/supply and milk release were indirectly monitored using body weight gain of pups during a timed-feeding period on postnatal Days 8/9 and 13/14. Plasma corticosterone, insulin, C-peptide, and prolactin were measured by radioimmunoassay in control, diabetic, and insulin-replaced diabetic animals. Insulin replacement was provided by means of an osmotic minipump implanted subcutaneously in the nape of the neck. In addition, several parameters of maternal behavior were monitored in order to determine whether diabetes affected maternal behavior and, therefore, whether such changes played a role in the alterations of lactation observed during diabetes. Diabetes significantly suppressed MS and MR. However, the decrease in MR, which was restored after partial insulin replacement, was a reflection of the reduced MS. There were no significant differences between the parameters of maternal behavior monitored in control and diabetic animals. Blood glucose in diabetic dams was significantly increased over that of controls. Although the levels of plasma glucose in the insulin-replaced groups were significantly lower than those of their uncontrolled diabetic counterparts, they also remained higher than that of controls. Corticosterone was not significantly altered after induction of diabetes. Insulin and C-peptide levels were significantly reduced in the uncontrolled diabetics; however, insulin levels were corrected in the insulin-replaced groups. Serum levels of prolactin decreased in all diabetic groups and insulin failed to restore these levels to those of control animals. In conclusion, it appears that diabetes decreases lactation through a suppressive effect on MS rather than on MR, with insulin replacement correcting for such deficiency. In addition, despite the lactogenic importance of glucocorticoids, prolactin and insulin demonstrated in vitro, lactation in vivo can be corrected without returning the levels of all three hormones to normal. The importance of another factor(s), such as normoglycemia, as essential to the observed defects, needs to be investigated.

Effects of various stressors on milk release in the rat

This study investigated the effect of four stimuli on milk release (MR), namely, sound, nociception, novelty, and restraint. The role of the ensuing adrenocortical response in the suppression of MR was also evaluated. Plasma corticosterone (CORT) levels were measured at 0 (basal), 15, 30, and 60 min during the suckling sessions to determine whether elevated CORT normally associated with stress could be inhibitory to MR. Compared to nonstressed lactators, dams exposed to sound demonstrated no suppression in MR, but a significant increase in plasma CORT. Pain did not alter milk yield and elevated CORT only at the end of the first hour of exposure. During novelty, MR was suppressed and again CORT was only elevated at the end of the sampling period. Restraint decreased milk yield and increased CORT. During novelty, MR appeared to be regulated by an adrenal factor, which remains to be identified. The peripheral opiates seem to be partially involved during restraint. In conclusion, not all types of aversive stimuli interfere with MR. Of those which do, different mechanisms seem to be implicated depending upon the nature of the stressor. Furthermore, reduced MR during stress is not a direct consequence of increased CORT.

Activation of the adrenal cortex or the peripheral sympatho-adrenomedullary system does not necessarily influence milk ejection in the rat.

Following a 5-h isolation period, primiparous rats have the same milk supply on days 8/9 and 13/14 post partum, yet in response to suckling they release a greater amount of milk at the latter time. Inasmuch as stress is known to inhibit lactation and handling of the pups is stressful to the dams, the question arose as to whether separation from pups before nursing constitutes a greater stress for the dam at the earlier stage of lactation. This possibility was explored in the present study: As an index of stress, changes in plasma corticosterone were measured from chronically cannulated dams. In addition, the role of adrenal hormones and the peripheral sympathetic nervous system in the regulation of milk ejection under these experimental conditions was assessed following bilateral adrenalectomy and treatment with pentolinium, a ganglionic blocker which does not cross the blood-brain barrier. Corticosterone pellets were implanted subcutaneously following adrenalectomy in order to maintain proper lactation. From the results obtained, lactators demonstrated a greater increase in plasma adrenocorticosteroid levels in response to nursing on day 8/9 than on day 13/14 post partum, but milk yield was significantly less at the earlier than at the later stage of lactation. Adrenalectomy in conjunction with corticosterone replacement pellets did not alter milk supply or milk release. The subsequent treatment with pentolinium did not affect milk ejection. Pups still ingested less milk on day 9 than on day 13/14. It is suggested here that the isolation/suckling condition imposed on lactators may be more stressful earlier in lactation. Inasmuch as removal of the adrenal hormones along with ganglionic blockade did not modify the amount of milk ingested by the pups, it is concluded that the smaller milk release observed on day 9 post partum does not result from a direct suppression by the adrenal hormones or by the peripheral sympathetic nervous system on milk ejection.

Mammary resistance: a possible controlling factor in milk ejection

At 8 and 13 days post partum, rats have the same total milk availability; yet, in response to suckling they release a greater amount of milk on day 13 than on day 8. Increased sensitivity to suckling in the more advanced lactators may result from a greater release of oxytocin or from changes in the mammary glands as lactation advances. The present study explores this latter possibility in anaesthetized dams at 8-9 and 13-15 days of lactation. Milk release and intramammary pressure were measured in anaesthetized dams in response to various doses of oxytoxin. Milk release was determined from the body weight gain of pups which had been fasted for 5 h before suckling on dams which had been isolated for 5 h. This parameter was significantly greater in 13- to 15-day lactators than in 8- to 9-day lactators over the range of oxytocin doses examined. In contrast, intramammary peak pressure and its dissipation time were significantly larger in the 8- to 9-day lactators than in the 13- to 15-day lactators. The compliance of the mammary glands was indirectly assessed at the two stages of lactation. When a constant pressure pulse was introduced into a cannulated gland, the resulting pressure peak was significantly greater in 8-day than in 13-day lactators, indicating a greater resistance in the former. Taken together, these results indicate that when endogenous oxytocin is inhibited (by anaesthesia) the greater milk release observed at the later stage of lactation in response to various doses of oxytocin may be due to a decline in mammary resistance as lactation progresses.

Investigation of the nature of the “stretch response” in suckling rats

The “stretch response” in suckling rats has commonly been used as an index of milk ejection and milk intake. In the current study, we have compared the behavior of pups suckling on dams with either full, empty or ligated mammary glands. In response to an IV bolus of oxytocin, pups suckling on both full and empty nipples displayed the characteristic stretch behavior. Lack of milk release from the latter nipples was confirmed by lack of weight gain by the pups. In contrast to pups suckling on intact nipples, those suckling on ligated nipples did not display the stretch response. It is concluded that this behavior occurs in response to erection of the nipple and is not necessarily associated with milk release.

Aspects of Intracellular Transit of Serum and Lipid Phases of Milk

Intracellular sites of origin of constituents of milk and mechanisms by which milk constituents are compartmentalized and transported to the apical cell surface for release into alveolar lumina have been studied by microscopists, physiologists, and cell biochemists over the past 25 or more yr. Through the efforts of these many investigators much has been learned about formation, transport, and secretion of milk constituents. However, the pace at which knowledge about milk formation has accumulated has been modest, and we have much to learn about the processes leading to formation and cellular release of milk. In view of the signal importance of lactation to mammalian life, it is regretable that so much remains to be learned about the differentiated mammary epithelial cell.

Regulation of milk ingestion in the infant rat

The aim of this study was to differentiate between maternal and offspring factors involved in the control of milk ingestion. Specifically, we investigated: (1) the temporal pattern of milk ingestion in fasted and non-fasted sucklings; (2) the amount of milk released as compared to that of milk available; and (3) the roles of the age of pups and the lactational stage of the dam as determinants of milk release. There were three general findings. First, the temporal pattern of milk letdown following a 5-hr accumulation consisted of an initial rapid phase followed by a slow “maintenance” phase. Second, a limiting factor in the amount of milk released is the dam's sensitivity to the suckling stimulus which changes as lactation progresses. Third, the age of the pups does not appear to play a determining role in milk release, but the degree of their deprivation does. In summary, it is suggested that compensation for weight loss during a fast in infant rats depends on an interplay between the pups' ability to increase their own intake, the milk availability, and the maternal sensitivity to suckling.

Individual patterns of milk intake during breast-feeding

The pattern of milk transfer during breast-feeding was ascertained for individual mother-infant pairs using a ‘fractional’ weighing technique. This method employs a single, fixed intermediate weighing on each breast, and a flexible, final weighing point at the ‘natural’ termination of feeding on each breast. The data demonstrate considerable variability between individuals both in feed length and in the rate of milk transfer from mother to baby. They show that the rate of intake tends to be consistent between the first and second breast, and that each mother-infant pair has a characteristic rate of milk transfer. Significant milk intake occurred from four minutes to the end of the feed on each breast. These results imply that breast-feeding ‘rules’ about the length of a feed can only be offered as helpful guidelines, rather than principles to be strictly followed. The results of a reciprocal nursing experiment suggest that the typical rate of milk transfer is a product of both milk release by the mother and milk demand by the baby.

Investigation of body temperature as a possible feeding control in the suckling rat

Under natural conditions, rat pups are deprived of milk only when the dam leaves the nest. At this time the body temperatures of the pups will fall. In this study we have investigated the possibility that lowered body temperature of the pups stimulates behavioral changes in either the pups or the dam, leading to increased milk intake. To study behavioral changes of the pups, the milk intake of warm-fasted, cool-fasted, and fed littermates was compared to 10, 14 and 16 days of age. There was no effect of body temperature on milk intake at any age. To study behavioral changes in the dam, milk release by dams suckling entire cool litters was compared with that by dams suckling entire warm litters. Milk release was not significantly affected by the litter temperature. We conclude that lowered body temperature of suckling rat pups does not cause increased milk intake.

Effect of Calf Calls on Rate of Milk Release of Dairy Cows

The effect of tape recorded vocalization of young calves on the rate of milk release was studied with 16 dairy cows. The reproduction of the calf calls started just as the cows were entering the milking parlor and ceased when the least teat cup had been placed on the 16th cow. Total stimulation per milking varied from 90 to 120s. To determine possible changes due to repetition and/or familiarization, the stimulation periods covered 1, 3, or 5 days, interchanging randomly with equally varying periods of nonstimulation. The experiment lasted 108 days and overall included an identical number of days of stimulation and nonstimulation. The measured response was the amount of milk released in the first 2min of milking. The 2-min milk yields increased slightly with days of stimulation. Variation between cows in their responsiveness to the stimulation, defined as the difference between periods of nonstimulation and stimulation, was relatively small.

Hormone Action: Oxytocin-Induced in vitro Milk Release

H ORMONE ACTION IS AN AREA of physiology that presents a challenge to instructors seeking economical procedures for demonstrating principles. The milk-ejecting activity of the neurohormone, oxytocin, on mammary gland tissue is a dynamic example of the mechanism of action of a hormone, yet it is simple and relatively inexpensive to demonstrate. The main physiological role of oxytocin, a hormone of the posterior pituitary gland of mammals (Linzell 1959), is to stimulate milk release from the mammary gland. Oxytocin is an example of a neurohormone because it is synthesized within neurons in the hypothalamus, an area of the lower part of the brain (diencephalon) responsible for the control of many physiological functions. Oxytocin is transported within these neurosecretory neurons to their neural endings in the posterior pituitary gland. The

The Breast: Morphology, Physiology, and Lactation

Scientific interest in functions of the breast is manifested by the increasing number of publications in both the clinical and investigative literature during the past decade. Nevertheless, there is probably no organ about which there is greater misinformation than the breast. The author has successfully summarized the basic information about structure and function of the breast (with emphasis on lactation and interrelated endocrine functions) and about disorders of the breast such as the syndromes of inappropriate lactation. In the first of nine chapters, the author discusses development of the breast from the fetal to the adolescent phase, although he does not provide detailed information about the mechanisms that govern the development of a prepubertal breast along female or male patterns. The second chapter deals mostly with the adult breast, anatomically and functionally, and describes the changes during pregnancy, and the factors controlling the synthesis and release of milk. The discussion

Differential effects of progesterone on lactation and nursing behavior in late pregnant and postparturient rats

In the past, studies on the effects of progesterone injections before or after birth concentrated only on lactation or nursing behavior. The present study is a report of the effects of progesterone on both events, in the same strain of rat, across a number of groups, administered either during pregnancy or after birth. In the first part of the experiment, 2 mg doses of progesterone subcutaneously were injected into nulliparous Sprague-Dawley rats from Days 18–23 of gestation. The injections delayed the onset of birth, caused a high mortality among young, and produced young that failed to thrive. In spite of this, nursing behavior appeared normal. There were no significant differences in the latency or duration of crouching behavior between the progesterone and oil-injected control groups. Thus the difficulties appeared to be with lactation. Because mammary glands contained milk, problems with secretory activation in the glands were ruled out. Even though the pups suckled teats, they got no milk, suggesting dysfunctions in milk release. To determine whether progesterone might alter maternal behavior once it was established after birth, 2-mg doses of progesterone were injected during the first postpartal week. They were found to depress litter weights and increase the latency to crouch over pups. During the second postpartal week, the injections reduced the latency to crouch, causing females to act vigorously toward pups at a time when maternal behavior typically starts to decline. Thus, depending upon the stage of the reproductive cycle in which progesterone is introduced, it can either inhibit or enhance nursing behavior. Moreover, the action of progesterone during late gestation appears to be only on milk release.

Influence of Repeated Oxytocic Treatments on Composition of Bovine Milk Fat

Fatty acid composition of bovine milk fat was not affected significantly by prolonged forced milk release. Monoglyceride content increased markedly with this treatment while phospholipid content was depressed slightly. Mastitis, as measured by the California Mastitis Test, Produced little effect on fatty acid composition of milk fat.

Secretory discharge and microflora of milk gland in tsetse flies

THE uterine or milk glands in tsetse flies (Glossina spp.) are modified female accessory reproductive glands which elaborate and release a nutritive liquid of proteinaceous and lipoid nature for the maturing intrauterine larva1–3. The multi-branched tubules of the gland converge into a pair of efferent ducts which fuse inside the oviductal shelf and open into the lumen of the uterus just posterior to the opening of the oviduct4,5. Cytological details of the milk gland and their modulations in relation to the state of pregnancy of the female have been described6 (W-C. M., D. L. D., D. S. Smith and U. Jarlfors, in preparation). Earlier work has suggested that milk is released directly into the lumen of the gland by apocrine secretion4. Our observations on the structure of the milk gland do not support such a mechanism, but rather, a novel type of exocrine discharge in which secretion is stored in an extracellular reservoir and released into the lumen through a dense cuticular network. At the points of milk release the lumen is frequently inhabited by bacteria which have not previously been described in milk glands. Our examination is based on milk glands from G. morsitans morsitans West-wood, but a comparative study using G. austeni Newstead and G. longipalpis pallidipes Austen has shown no essential differences among the three species.

Distribution Changes in Bovine Skimmilk Proteins During Forced Milk Release

The concentration of caseins and serum proteins in bovine skimmilk decreased when cows were maintained under the prolonged influence of oxytocin. Resolution of the components of these fractions by disc electrophoresis indicated that α-casein and α-lactalbumin decreased during forced milk release whereas β-casein and blood serum albumin increased.

Effects on lactation of progesterone injections administered during late pregnancy in the rat.

SummaryProgesterone injections administered during late pregnancy effectively inhibit lactation in the rat. Subcutaneous doses of 0.5 and 2 mg of progesterone in sesame oil twice daily between days 18 and 23 of gestation produced a greater inhibitory effect than 0.1 mg of progesterone similarly administered, particularly with regard to mortality and weight changes of the young, and the release of milk in nursing tests. The primary inhibition appears to rest on processes of milk ejection rather than milk secretion or the motivation to nurse.