RGD Reference Report - Mammary gland copper transport is stimulated by prolactin through alterations in Ctr1 and Atp7A localization. - Rat Genome Database

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Mammary gland copper transport is stimulated by prolactin through alterations in Ctr1 and Atp7A localization.

Authors: Kelleher, SL  Lonnerdal, B 
Citation: Kelleher SL and Lonnerdal B, Am J Physiol Regul Integr Comp Physiol. 2006 Oct;291(4):R1181-91. Epub 2006 Jun 1.
RGD ID: 1599391
Pubmed: PMID:16741141   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpregu.00206.2005   (Journal Full-text)

Milk copper (Cu) concentration declines and directly reflects the stage of lactation. Three Cu-specific transporters (Ctr1, Atp7A, Atp7B) have been identified in the mammary gland; however, the integrated role they play in milk Cu secretion is not understood. Whereas the regulation of milk composition by the lactogenic hormone prolactin (PRL) has been documented, the specific contribution of PRL to this process is largely unknown. Using the lactating rat as a model, we determined that the normal decline in milk Cu concentration parallels declining Cu availability to the mammary gland and is associated with decreased Atp7B protein levels. Mammary gland Cu transport was highest during early lactation and was stimulated by suckling and hyperprolactinemia, which was associated with Ctr1 and Atp7A localization at the plasma membrane. Using cultured mammary epithelial cells (HC11), we demonstrated that Ctr1 stains in association with intracellular vesicles that partially colocalize with transferrin receptor (recycling endosome marker). Atp7A was primarily colocalized with mannose 6-phosphate receptor (M6PR; late endosome marker), whereas Atp7B was partially colocalized with protein disulfide isomerase (endoplasmic reticulum marker), TGN38 (trans-Golgi network marker) and M6PR. Prolactin stimulated Cu transport as a result of increased Ctr1 and Atp7A abundance at the plasma membrane. Although the molecular mechanisms responsible for these posttranslational changes are not understood, transient changes in prolactin signaling play a role in the regulation of mammary gland Cu secretion during lactation.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lactation  IEP 1599391; 1599391 RGD 
response to prolactin  IEP 1599391 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
apical plasma membrane  IDA 1599391 RGD 
late endosome  IDA 1599391; 1599391 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Atp7a  (ATPase copper transporting alpha)
Atp7b  (ATPase copper transporting beta)


Additional Information