Copper transport to mammary gland and milk during lactation in rats

Donley, Stephanie; Ilagan, Bernard J.; Rim, Hisun; Linder, Maria C.

doi:10.1152/ajpendo.00115.2002

Cited by 40 publications

(55 citation statements)

References 53 publications

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“…This possibility is consistent with the protective role of ATP7A proposed above. It is also consistent with the results of Donley et al that in lactating rats, all newly absorbed copper is directed preferentially to the mammary gland where it is delivered at a higher concentration into milk [18]. Thus it is probable that there is a sufficient flux of copper into mammary epithelial cells to produce the observed trafficking of the Cu-ATPases.…”

Section: Discussionsupporting

confidence: 91%

“…The fact that the milk still contains about 25% normal copper levels suggests that a significant amount of copper reaches the milk by an ATP7B-independent mechanism. A possible source of this additional copper is the Cu-protein ceruloplasmin, which is known to be synthesized in the mammary gland and excreted in the milk [18,25]. Normally, it is thought that ceruloplasmin would receive copper in the TGN from ATP7B [26].…”

Section: Discussionmentioning

confidence: 99%

“…More recently, in the rat lactating mammary gland epithelial cells, Atp7a was found through the cell, but suckling resulted in greater staining at both the basolateral and apical plasma membranes [17]. Given that the uptake of copper is increased in the mammary gland of lactating rats [18] it is possible that the relocalization of both proteins is caused by the rapid entry of copper into the epithelial cells, but lactational hormones may also play a role [17].…”

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confidence: 99%

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Copper transport during lactation in transgenic mice expressing the human ATP7A protein

Llanos

Michalczyk

Freestone

et al. 2008

Biochemical and Biophysical Research Communications

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Both copper transporting ATPases, ATP7A and ATP7B, are expressed in mammary epithelial cells but their role in copper delivery to milk has not been clarified. We investigated the role of ATP7A in delivery of copper to milk using transgenic mice that over-express human ATP7A. In mammary gland of transgenic mice, human ATP7A protein was 10-to 20-fold higher than in control mice, and was localized to the basolateral membrane of mammary epithelial cells in lactating mice. The copper concentration in the mammary gland of transgenic dams and stomach contents of transgenic pups was significantly reduced compared to non-transgenic mice. The mRNA levels of endogenous Atp7a, Atp7b, and Ctr1 copper transporters in the mammary gland were not altered by the expression of the ATP7A transgene, and the protein levels of Atp7b and ceruloplasmin were similar in transgenic and non-transgenic mice. These data suggest that ATP7A plays a role in removing excess copper from the mammary epithelial cells rather than supplying copper to milk.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Copper transport during lactation in transgenic mice expressing the human ATP7A protein

Llanos

Michalczyk

Freestone

et al. 2008

Biochemical and Biophysical Research Communications

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“…Fpn is located in mammary epithelial tissue and likely required for iron transport into secretory vesicles for export to milk . A major diversion of newly ingested copper is delivered to the mammary gland, as opposed to liver, in lactating rats (Donley et al 2002). This may be to provide copper for milk but also to supply copper for other functions such as a putative "mammary ferroxidase".…”

Section: Discussionmentioning

confidence: 99%

Multiple mechanisms account for lower plasma iron in young copper deficient rats

Pyatskowit

Prohaska

2007

Biometals

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Copper deficiency lowers brain copper and iron during development. The reduced iron content could be due to hypoferremia. Experiments were conducted to evaluate plasma iron and "ferroxidase" hypotheses by determining copper and iron status of Holtzman albino rats following gestational/ lactational copper deficiency. Copper deficient (Cu−) dams on treatment for 5 weeks, two of gestation and three of lactation, had markedly lower copper content of milk and mammary tissue, and lower milk iron. Newborn pups from Cu− dams had lower copper and iron concentrations. Compared to Cu+ pups, Cu− pups, analyzed between postnatal age (P) 0 and P26, were smaller, anemic, had lower plasma iron, cardiac hypertrophy, and near zero ceruloplasmin activity. Liver copper in Cu+ pups increased then decreased during development and major reductions were evident in Cu− pups. Liver iron in Cu+ pups decreased with age while nursing but increased after eating solid food. Liver iron was lower in Cu− pups at P0 and P13 and normal at P20 and P26. Small intestinal copper decreased with age in Cu+ pups and was lower in Cu− pups. Intestinal iron levels in Cu-pups were higher than Cu+ pups postweaning in some experiments. Reduction in plasma iron in Cu− pups is likely due to a decreased "ferroxidase" function leading to lower placental iron transport, a lower milk iron diet, and partial block in iron uptake from intestine but is not due to failure to mobilize hepatic iron, in contrast to older rats eating diet with adequate iron.

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“…It has recently become appreciated how remarkable the change in Cu metabolism is during lactation. For example in rats, normally most absorbed Cu is first taken up by liver but when lactation occurs Cu is diverted to the mammary gland, presumably for milk Cu excretion (Donley et al, 2002). Cu deficiency in mice reduced milk Cu content by 85% (Prohaska, 1989).…”

Section: Discussionmentioning

confidence: 99%

Rodent brain and heart catecholamine levels are altered by different models of copper deficiency

Pyatskowit

Prohaska

2007

Comparative Biochemistry and Physiology Part C: Toxicology &

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Limiting dopamine β-monooxygenase results in lower norepinephrine (NE) and higher dopamine (DA) concentrations in copper-deficient (Cu−) tissues compared to copper-adequate (Cu+) tissues. Mice and rat offspring were compared to determine the effect of differences in dietary copper (Cu) deficiency started during gestation or lactation on catecholamine, NE and DA, content in brain and heart. Holtzman rat and Hsd:ICR (CD-1) outbred albino mouse dams were fed a Cu-diet and drank deionized water or Cu supplemented water. Offspring were sampled at time points between postnatal ages 12 and 27. For both rat and mouse Cu-tissue, NE and DA changes were greater at later ages. Though Cu restriction began earlier in rats than mice in the gestational model, brain NE reduction was more severe in Cu-mice than Cu-rats. Cardiac NE reduction was similar in Cu-rodents in the gestation models. In the lactation model, mouse catecholamines were altered more than rat catecholamines. Furthermore, following lactational Cu deficiency Cu-mice were anemic and exhibited cardiac hypertrophy, Cu-rats displayed neither phenotype. Within a species, changes were more severe and proportional to the length of Cu deprivation. Lactational Cu deficiency in mice had greater consequences than in rats.

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Copper transport to mammary gland and milk during lactation in rats

Cited by 40 publications

References 53 publications

Copper transport during lactation in transgenic mice expressing the human ATP7A protein

Copper transport during lactation in transgenic mice expressing the human ATP7A protein

Multiple mechanisms account for lower plasma iron in young copper deficient rats

Rodent brain and heart catecholamine levels are altered by different models of copper deficiency

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