Suckling results in the firing of afferent impulses via the anterolateral columns of the spinal cord to the brain stem and hypothalamus. The hypothalamus subsequently decreases release of dopamine (formerly described as prolactin inhibitory factor) into the portal circulation to the pituitary gland. It was postulated that a dopamine-stimulating factor existed but, although several hormones positively modulate prolactin secretion, control is largely by the lifting of the tonic inhibition from dopamine. The abrogation of thedopamine inhibition stimulates the release of prolactin from the cells of the anterior pituitary. Secretion of prolactin is modified by oestrogen and thyroid-stimulating hormone (TSH). Studies in rats have demonstrated that vasoactive intestinal peptide (VIP), released from the pituitary gland, is an extremely potent prolactin-releasing factor and affects mammary blood flow. The number of signals affecting prolactin release indicates a complex neuroendocrine axis (Ben-Jonathan et al., 1991). β-Endorphin and melanocyte-stimulating hormone (MSH), which are co-released from the intermediate lobe of the pituitary gland, also seem to have a role. β-Endorphin blocks dopamine inhibition of prolactin and MSH stimulates the release of prolactin by lowering the threshold of the lactotrophs (Porter et al., 1994).

Levels of prolactin begin to rise within 10 min of suckling, peak about 30 min after initial stimulation and then progressively fall back to basal levels within a further 3 h. This delay in prolactin secretion following suckling led to the concept that the rise in prolactin was the ‘order for the next meal’. Areolar stimulation is essential for prolactin release; negative pressure alone is not adequate and denervation of the nipple prevents prolactin release in response to nipple stimulation.

Prolactin levels fall abruptly about 2 h before delivery then dramatically rebound. These fluctuations in prolactin level probably relate to changing oestrogen concentrations. The level of prolactin seems to be important in establishing lactation but levels are much diminished after 6 weeks at a rate dependent on suckling frequency and duration (Johnston and Amico, 1986). The peak prolactin levels in response to suckling also fall progressively.

Prolactin has a pulsatile release. A diurnal rhythm of prolactin secretion is apparent, with higher circulating levels during sleep. The exact quantitative relationship between prolactin levels and milk production is not clear. In the early puerperium bromocriptine, a dopamine D₂ receptor agonist causes a fall in prolactin levels and abolishes milk secretion. Dopamine-receptor blockers (such as metoclopramide, haloperidol, domperidone and sulpiride) increase prolactin levels and milk production. The use of drugs which stimulate prolactin should be the last resort after excluding all the other factors which might negatively affect milk supply such as checking the positioning of the infant. All the drugs are a risk of side effects. Domperidone is usually preferred because it has a lower risk of toxicity as it crosses into the breast milk and brain to a lesser extent (it has a large molecular weight, is less soluble and is usually bound to proteins). Dopamine binds to receptors on the pituitary and is internalized resulting in the increased breakdown of prolactin within the secretory granules. However, women who have had pituitary surgery and have prolactin levels just above non-pregnant level can breastfeed. The evidence seems to suggest that a threshold prolactin level is required but then there is no correlation between prolactin level and milk production (Howie et al., 1980).

Prolactin binds to receptors on the secretory alveolar (acinar) cells acting at several sites to increase synthesis of several components of the milk including casein, lactalbumin and fatty acids. During pregnancy, secretory alveolar cells proliferate and acquire the characteristics of highly active secretory cells including numerous mitochondria, an extensive endoplasmic reticulum, well-developed Golgi apparatus and many secretory vesicles. Early suckling is important to stimulate prolactin to ensure that milk production is optimal and sustained. Infrequent and/or poor suckling in the early postnatal period may significantly reduce the optimal long term milk production as less prolactin receptor complexes are formed so stimulation of the acinar cells is sub-optimal and the potential for milk production is reduced (Manuel et al., 2007). It is important to support and reassure mothers whose infants frequently suckle in the early postnatal period to promote prolactin release and establish long term breast feeding (Case Study 16.1). Introduction of formula feeds in the belief that the infant is hungry will interfere with the establishment of lactation. In the first few hours of birth, spontaneous suckling may be facilitated by maternal–neonatal skin-to-skin contact (Bramson et al., 2010).

As well as the dopamine-antagonist drugs, there are a number of herbal galactogogues which have been traditionally used to promote milk production; these include fenugreek seeds, fennel, brewer’s yeast, alfalfa, asparagus, rescue remedy and ignatia 6x (Gabay, 2002). There is a lack of scientific evidence for the effectiveness of these herbal galactogogues. Smoking has been shown to reduce prolactin production (Andersen et al., 1984); in addition, psychosocial factors tend to result in lower rates of breastfeeding in women who smoke (Amir and Donath, 2003).

The secretory cells of the alveoli (Fig. 16.3) synthesize or extract the components of milk, which are secreted into the alveolar lumen. The cells are joined near their apical surface by adherins and tight junctions. The apical plasma membrane has a smooth surface with few microvilli, in contrast to the tightly folded basal membrane, which facilitates uptake of substrates such as amino acids, glucose, acetate and fats from the extracellular space. Proteins, fats and lactose are synthesized in the cell and packaged into vesicles. The vesicles move to the apex of the cell where exocytosis takes place.

The composition of the maternal diet can influence the components of breast milk, especially those passing from blood to milk with little modification by the alveolar cell, such as lipids. The alveolar cells have a unique mechanism for lipid secretion whereby microlipid droplets coalesce forming progressively larger lipid droplets that are eventually enclosed by a specialized milk fat droplet membrane prior to secretion (McManaman and Neville, 2003). Aqueous solutes including the proteins, oligosaccharides, lactose, citrate, phosphate and calcium are secreted into the milk by exocytosis after being packaged into secretory vesicles by the Golgi apparatus. Macromolecular substances derived from maternal serum, such as serum proteins (IgA, albumin and transferrin), endocrine hormones (insulin, prolactin and oestrogen), cytokines and lipoprotein lipase, are transported by a transcytosis pathway. Various membrane transport pathways transfer small molecules and ions such as glucose, amino acids and water. Large blood cells and serum follow a paracellular route, squeezing between the alveolar cells.

Oxytocin levels control the milk ejection reflex, which is responsible for the transfer of the milk from the breast to the baby. Oxytocin stimulates the myoepithelial cells so the alveolar sacs are compressed, increasing the pressure, and the ducts shorten and widen. Although secretion of oxytocin is under a similar neuroendocrine reflex to prolactin, it is physiologically independent. Oxytocin synthesis in the hypothalamus, and its release from the posterior lobe of the pituitary gland, is increased in response to handling the baby, hearing cries or thinking about feeding as well as by tactile stimulation at the nipple. Oxytocin is released in short-lived bursts of less than a minute immediately in response to stimuli. Frequently, the largest response is to the baby crying before feeding so maximum release of oxytocin may occur before suckling even starts. Between feeds, isolated pulses of oxytocin are released (McNeilly, 2001) possibly in response to other babies’ cries or fleeting images of the baby. Unlike prolactin secretion, the milk ejection reflex can be conditioned, as demonstrated by dairy farmers who clang their buckets to stimulate oxytocin and a good milk yield. Similarly, a baby’s cry can often trigger oxytocin secretion, which is why the practice of babies ‘rooming-in’ with their mothers (sleeping close to their mother’s bed) is often associated with successful breastfeeding.

The milk ejection reflex is very sensitive to inhibition by physical and psychological stresses such as pain and discomfort, anxiety, emotional swings, tiredness, embarrassment, worry and alcohol. Women who have had long labours, high levels of intervention and traumatic deliveries may be particularly at risk of impaired oxytocin production. In addition, the use of oxytocin to augment labour may reduce endogenous oxytocin levels in the early postnatal period and also affect the milk ejection reflex (Jonas et al., 2009). The limbic system, which coordinates the body’s responses to emotions, is involved in oxytocin release. The likely mechanism is catecholamine inhibition of oxytocin release and adrenergic vasoconstriction of mammary blood vessels limiting access of the oxytocin to the myoepithelial cells. Women experiencing problems in establishing milk flow are often helped by covering their breasts with warm flannels which appears to aid blood flow and oxytocin access. Women may be embarrassed by exposing their breasts or being touched by practitioners helping them to establish breastfeeding and so a ‘hands-off’ approach is best adopted whilst focusing on maintaining privacy and dignity and minimizing inhibition. Stress reducing interventions such as relaxation therapies and skin-to-skin contact have been shown to improve lactation performance (Lau, 2001).

Surprisingly, denervation of mammary glands in experimental animals appears to have little effect on milk production (Williams et al., 1993). This suggests that the afferent nerve pathway may not be as important as the interactions of neurotransmitters. Transmitters that have been implicated in the control of the milk ejection reflex include noradrenaline, β-endorphin, serotonin and dopamine. As with control of prolactin secretion, the number of factors influencing oxytocin secretion suggests that the pathway is much more complicated than originally thought. Stimulation of the female reproductive tract, especially the vagina and cervix, increases oxytocin release so milk may be ejected from the breasts during coitus.

Oxytocin binds to specific receptors on the myoepithelial cells around the milk-secreting cells and to longitudinal cells in the duct walls. Contraction of the myoepithelial cells results in milk being expelled into the ducts, which shorten as the longitudinal cells contract. Oxytocin-induced contraction generates pressure waves within the breasts and is responsible for prickly sensations associated with breastfeeding. When the milk ejection reflex is well established, milk may be spontaneously ejected from both breasts.

Oxytocin pulses increase in amplitude during labour and are involved in the positive-feedback amplification in labour (see Chapter 1). Oxytocin is associated with changes in maternal behaviour and increased alertness at delivery. The pulses of oxytocin induced by feeding have an effect on the uterus, stimulating uterine contractions and involution. Multiparous women tend to feel these contractions or ‘after-pains’ with increased intensity. Women who do not want to breastfeed may find the physiological changes in the breasts at delivery uncomfortable; various techniques are recommended to inhibit lactation (Box 16.3).

Most problems have an identifiable physiological basis; breast milk insufficiency is frequently over-diagnosed and is usually simply resolved (Woolridge, 1996). The majority of women with apparently insufficient milk supply have unsubstantiated worries and require confidence, improved technique (especially positioning), encouragement or advice. This can be supported by physiological strategies such as electric breast pumps and pharmacological (anti-dopamine) agents. Avoiding pressure on the breasts (such as that due to wearing a tight bra or other tight clothing or sleeping prone) is important as it can negatively affect milk supply. Iatrogenic low milk supply may be attributed to excessive down-regulation of supply probably during the calibration period. It is possible that baby milk manufacturers inadvertently exploit the importance of the calibration period by offering free milk samples early in lactation. If the initial calibrated volume cannot be increased, the mother will then be unable to increase her milk supply later and will be forced to provide alternative inferior sources of milk, which are expensive and can be harmful if water supplies are contaminated, as happens in a number of developing countries.

Behavioural problems that are acquired by the baby as coping strategies to avoid aversive events may also induce a low milk supply. These problems include discomfort during positioning at the breast and problems with breathing. Self-limitation of intake and lack of persistence may account for the condition described as ‘contented underfed babies’ (Woolridge, 1996). Pathophysiological failure is rare and probably affects less than 2% of women with apparent milk insufficiency. Rare causes include mammary hypoplasia, or absence of normal breast development at puberty or in pregnancy. Retained placental products affect lactation reversibly but Sheehan’s syndrome, necrosis of the anterior pituitary due to acute hypovolaemic shock, as in antepartum haemorrhage (e.g. due to placental abruption) or postpartum haemorrhage, is more serious.

Many drugs are secreted into breast milk, but the data on the effects of specific drugs on the breastfed infant is often not available. Of particular concern are those drugs with central nervous system (CNS) activity as the postnatal development of the infant’s nervous system is vulnerable. The benefits of maternal treatment and the advantages of breastfeeding have to be balanced against the risk of exposure of the neonate to the medication. Passive diffusion of the unbound, unionized form of the drug into the breast milk is the major mechanism of transfer. Therefore, it is affected by maternal compartmentalization and molecular properties and the composition of the breast milk (McManaman and Neville, 2003). Assessment of adverse drug reactions in infants is difficult. Drugs that are minimally excreted into the breast milk, are metabolized quickly by the neonate and are not associated with adverse effects are obviously the preferred choice.

Socially used drugs such as alcohol (Mennella and Beauchamp, 1991), nicotine and illicit drugs (heroin and cocaine) (Golding, 1997) also cross into the milk. How much these affect the baby is not clear. Women who smoke are less likely to want to breastfeed, or initiate breastfeeding, and more likely to breastfeed for a shorter duration (Amir and Donath, 2003). Drug metabolism and elimination by the neonate is often limited, so exposure to apparently low doses of the drug in milk can have a cumulative effect, particularly in premature babies and those who have prolonged exposure. Drugs tend not to accumulate in the milk but have a bidirectional transfer. Therefore, the amount of drug received by the infant will be reduced if the mother takes the drug immediately after a feed so the baby does not feed when the drug is at peak concentration in the maternal plasma and milk. Production of breast milk is also a method of excretion and contains drugs, viruses, food additives, chemical contamination (such as lead), volatile solvents, pesticides and radioactivity. Chemical residues of pollutants are detected in most human milk throughout the world. Heavy metals are of concern because of the susceptibility of the infant’s nervous system. Mammals do not have a mechanism to excrete pesticide residues such as polychlorinated biphenyls and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT). However, the residues do cross the blood–breast barrier so lactation is the only way to reduce the body load. The burden of persistent organic pollutants is then transferred to the breastfed infant (Nickerson, 2006). Usually, breastfeeding is not contraindicated but a slow and steady rate of maternal weight loss during lactation is important to limit the mobilization of maternal fat and release of the environmental contaminants which can then partition in the breast milk.

Women often cease breastfeeding prematurely in the first 6 months after birth because they experience breastfeeding related problems such as pain, cracked nipples, milk stasis and mastitis (Abou-Dakn et al., 2009). These conditions may occur in isolation or may be compounded by anxiety about milk sufficiency. It is estimated that a significant proportion of breastfeeding women will experience some problem in the first few days of feeding. Women experiencing breastfeeding problems are likely to have a higher level of psychological stress. Although lactation may be protective against stress in the short-term, longer lasting psychological stress may negatively affect the endocrine, immune and nervous systems (Wöckel et al., 2010).

Maternal viruses may enter the milk. Vertical transmission and subsequent infection of the infant via breast milk have been confirmed for human immunodeficiency virus (HIV), tuberculosis (TB), cytomegalovirus (CMV) and hepatitis B. It is probably inadvisable for mothers with TB to breastfeed as the infection tends to be reactivated by maternal tiredness and stress (Box 16.4). However, advice for HIV-positive mothers is unclear. The immunological properties of breast milk are probably important in protecting against illnesses that accelerate the development of AIDS (acquired immune deficiency syndrome), particularly in areas of the world where it is endemic (Van de Perre, 1995). The likelihood of HIV transmission is affected by maternal viral load, the volume of the milk consumed, the duration of breastfeeding, inflammation of the breast (e.g. caused by cracked nipples), the presence of oral thrush and the introduction of formula milk (Warner and Sapsford, 2004). (Note that several medications used in HIV prophylaxis can transfer to the breast milk and have potentially serious side effects, including anaemia, seizures, hepatitis and feeding difficulties.) The WHO recommends exclusive breastfeeding for the first 6 months of life (and breastfeeding with complementary feeding for the first 2 years of life). The rationale for this is the protective effect of breastfeeding on infection rate. However, in developed countries where the water supply is clean and good quality, alternatives to breast milk are feasible and affordable, it may be preferable for mothers with serious infections not to breastfeed to prevent vertical transmission. However, it should be noted that whatever method is chosen, it should be exclusive as mixed feeding is thought to increase the risk of transmission of HIV.

Case study 16.2 is an example of concerns about breastfeeding.

The energy output of milk is a significant proportion of the total energy output of the lactating woman; it is suggested that peak lactation requires an increase of energy intake of about 25%. In dairy animals, the level of food intake strongly correlates with milk yield. In a number of species, lactation results in a significant increase in size and complexity (such as villus size) of the maternal intestine (Hammond, 1997), but it is obviously not possible to study any such adaptive changes in lactating women. It may not be valid to apply knowledge of nutrition and physiology of dairy animals, which are completely milked twice a day, to mammals that suckle their young according to natural patterns of behaviour. Anthropological studies on human hunter–gatherer communities suggest that babies feed every half hour at 2 weeks and every 4 h at 4 months. The characteristics of mammalian milk relate directly to the interaction between the mother and child. Marsupials and animals that bear their young during hibernation are always present and produce milk that is dilute and has a low fat content. In contrast, in animals where the mother nurses her young at widely spaced intervals, for instance a hunting lioness, the milk is very concentrated and high in fat. Human milk has most resemblance to the former; it is dilute with a low fat content suggesting that humans have evolved as a species where the young have unlimited access to milk and there is high attentiveness shown by a constantly present mother (Prentice and Prentice, 1995). The stress of human lactation is relatively low compared with species with faster growing or multiple young, but this is countered by the high cost of maintaining a dependent infant for a prolonged period. The high level of maternal investment in pregnancy and slow reproductive cycle mean that humans are committed to sustain a conception.

There is a discrepancy between the theoretical calculated energy requirement for milk production and the actual intake of lactating women, even taking into account the fat reserves laid down in pregnancy. Current recommendations are that an exclusively breastfeeding woman requires an additional 2700 kJ (650 kcal) per day and an increase of 20 g of protein per day (Dewey, 1997). However, it is thought that about 600 kJ (150 kcal) per day will be provided by the maternal fat stores for the first 6 months so the net increment needed is 2100 kJ (500 kcal) per day. In practice, these requirements are much higher than the observed intakes in successfully lactating women even when offered unlimited access to food. Lactational performance is particularly resilient in humans as demonstrated by the efficiency of lactation in undernourished and impoverished communities. In animals, a decrease in non-shivering thermogenesis (inhibition of brown-fat heat generation) (NST) and therefore the provision of extra energy for milk production are suggested to account for this difference. The mechanism in humans is not thought to be mediated by changes in NST but the lactating woman has increased sensitivity to insulin (Illingworth et al., 1986). This energy-sparing effect and efficient energy utilization of lactating women have a particularly big implication in developing countries.

Increased incidence of obesity in Western societies is of concern with about a third of women having a body mass index (BMI) greater than 25 kg/m². Pregnancy is a risk factor for the development of obesity; it is suggested that postpartum weight loss may not be inevitable and gestational weight gain may not be lost postpartum (Chin et al., 2010). Possibly, the changes in energy metabolism associated with pregnancy and lactation may remain after weaning. If so, lactation could contribute to the problem. Different species of mammal lay down body fat during pregnancy to different degrees. In lactation, mammals rely on the deposited fat to different extents. Whales and seals, for instance, rely entirely on body fat and protein reserves to sustain lactation whereas dairy cows and laboratory rats are very dependent on increased intake to provide energy for milk yield. Pregnant women deposit fat and have a changed hormonal environment. The reported studies tend to conflict and do not show significant differences in weight loss with different patterns of infant feeding. However, interpretation of the studies is confused by confounding factors such as different duration and extent of feeding and the increased tendency of women who are not breastfeeding to reduce their weight deliberately. There is also a large variation in the energy content of the milk produced (see below). Lactating women produce adequate-to-abundant quantities of milk of sufficient quality to promote growth of healthy infants, even when maternal nutrition is not adequate. Whereas the health of the breastfeeding infant is apparently protected should maternal nutrition be compromised, it is probably at the cost of depletion of maternal nutrient stores and potential effects on subsequent pregnancies. Deliberate weight loss in well-nourished healthy breastfeeding woman has no effect on the yield or composition of breast milk. However, it is recommended that weight loss should not be more than 1–2 kg per month (Institute of Medicine, 2002). Although reduction in energy intake does not affect milk synthesis, lower intakes of food mean that micronutrient intake, particularly calcium and vitamin D, might be compromised (Lovelady et al., 2006). As energy intake falls, the likelihood of a number of nutrients failing to reach the recommended intake progressively increases. In order of vulnerability, the nutrients most likely to be affected are calcium, zinc, magnesium, thiamin, vitamin B₆, vitamin E, riboflavin, folate, phosphorus and iron (Lawrence, 2010). Overweight lactating women are advised to restrict their energy intake by decreasing consumption of foods high in simple sugars and fat and by increasing their intake of calcium-rich foods, vegetables and fruit.

Both pregnancy and lactation present a tremendous challenge to maternal calcium status (Prentice, 2000). The fetal skeleton requires 5 mmol of calcium per day. The lactational drain of calcium is greater; average daily production of 800mL milk contains 6.25 mmol of calcium. It is estimated that about 10% of total maternal calcium stores (about 105 g) is transferred to the fetus/neonate, predominantly duration lactation (Wysolmerski, 2002). One or more of the following can meet demand for calcium: increased dietary calcium, increased absorption, decreased excretion or increased bone demineralization (net loss of bone). In the third trimester, absorption of calcium increases together with a modest increase in bone resorption. This increase in calcium absorption appears to be independent of vitamin D status (Fudge and Kovacs, 2010). Calcium demands of lactation are met by an increase in the rate of bone resorption and a decrease in renal calcium excretion which are speculated to have evolved from the adaptations in bone and mineral metabolism that supply calcium for egg production in lower vertebrates (Wysolmerski, 2002). The oestrogen level during lactation is relatively low so the bone mass is not protected to the same extent.

Lactation is the period of most rapid bone loss in a woman’s life; there is a net drain of calcium from the body, with a selective decrease in trabecular bone. This reduction is independent of parathyroid hormone and vitamin D levels. So lactation may appear to increase future risk of osteoporosis, but risk factors shown to be associated with fractures do not necessarily include breastfeeding (Sowers, 1996). During weaning, an imbalance between bone resorption and bone formation results in a rapid and complete recovery of bone mass. The implications for birth spacing and prolonged breastfeeding are not clear. Modern practices of delaying childbearing resulting in decreased time for recovery before menopause are probably countered by the cumulative effect of having fewer children. Prolonged lactational amenorrhoea may help to restore maternal iron status.

The mammary gland homeostatically controls milk concentration of essential nutrients; levels of major minerals including calcium, sodium, potassium, phosphorus and magnesium are not affected by the diet. The mammary gland can adapt to maternal deficiency (or excess) of iron, zinc and copper (Lönnerdal, 2007) suggesting there are active transport mechanisms for these nutrients in the mammary gland. When milk production falls during weaning, milk iron levels decrease and milk zinc levels increase. However, maternal intakes of iodine and selenium do affect levels in milk. As iodine is so important for fetal and neonatal brain and nervous system development and many women do not have an optimal intake of iodine (partly because salt use is decreasing and fewer iodine-containing cleaning agents are used in the dairy industry), iodine supplements are widely recommended for pregnant and lactating women and for women considering pregnancy (Zimmermann, 2009).

The volume of milk produced is robust; only very severe dehydration and extreme malnutrition affect the volume of milk produced. There is no evidence that increasing fluid intake increases the volume of milk produced or that reducing fluid intake prevents engorgement. When fluids are restricted, urine output decreases and the woman is at risk of dehydration. Breastfeeding women should be advised to drink when they are thirsty and to be aware that they will need more fluid than normal.

In the first 3 days postdelivery, the mother produces about 2–10mL of colostrum per day. More colostrum is produced sooner if the woman has had previous pregnancies, particularly if she has lactated before. In some cultures, colostrum is thought to be old milk or ‘pus’ and is discarded rather than fed to infants.

Colostrum is transparent and is yellow from the high β-carotene content. Mature milk in contrast looks less viscous and slightly blue. Colostrum has more protein and vitamins A and K and less carbohydrate and fat than mature milk. It is easily digested and well absorbed. It has a lower energy content of 58 kcal per 100mL compared with 70 kcal per 100mL in mature milk. Levels of sodium, potassium, chloride and zinc are high in colostrum but these reflect the low volume produced rather than the infant’s requirements for a bolus dose of certain nutrients. The composition is extremely variable, which reflects its unstable secretory pattern.

Colostrum facilitates the colonization of the gut with Lactobacillus bifidus (Wharton et al., 1994). Meconium also contains growth factors for L. bifidus. Colostrum seems to have a laxative effect, stimulating the passage of meconium. The high protein content is largely due to the abundant antibodies, which protect against gastrointestinal tract infection. IgA forms 50% of the protein content of colostrum, falling to 10% by 6 months. In the first few days of life, priming and maturation of the mucosal immune system is maximal and the gut is permeable and able to absorb macromolecules; colostrum contains many immunomodulatory molecules particularly anti-inflammatory agents which help to protect the vulnerable immature gut from mucosal damage.

During the first 30 h or so, the secretion (colostrum) has a high protein:lactose ratio. In the following days, as the baby suckles more and stimulates milk production, the resulting increase in prolactin secretion stimulates production of the major whey protein α-lactalbumin, which is a specific component of the enzyme lactose synthetase and so regulates lactose production. The effect of increasing lactose production is that water is drawn into the secretion to maintain osmotic equilibrium so the volume increases thus diluting the protein content. The absolute amounts of protein secreted into the milk are maintained or increased even though the concentration falls.