The 10‐20‐fold increase in basal copper uptake by mammary gland in lactation is not induced by lactational hormones

Abstract

As first shown in rats, the uptake of Cu by the mammary gland increases about 20‐fold over that in the virgin state in lactation, after i.p. or i.v. injection of tracer 64Cu. We hypothesized that this was due to the upregulation of Cu transporters and/or uptake systems/processes induced by lactational hormones. This was tested in the PMC42 cell model of human breast, which responds to lactational hormones by production of milk proteins and trafficking of Cu pumps, ATP7A and B; as well as in mouse mammary explants exposed to the hormones. 64Cu was delivered to the PMC42 cells grown in bicameral chambers by either pure human albumin, alpha‐2‐macroglobulin, or as the dihistidine complex. Pretreatment with a regimen of pre‐lactational and lactational hormones induced casein production but made no difference to initial rates of Cu uptake from any of the complexes. The same results were obtained with polarized monolayers with tight junctions, organoids produced with extracellular matrix, and with cultured mammary explants. Measurements of 64Cu uptake by mammary gland and other tissues of mice throughout pregnancy and into lactation indicated a strong positive relationship between initial rates and mammary gland mass. We conclude that increased mass rather than changes in expression of uptake systems may be the main determinant of mammary gland Cu uptake, at least in the absence of suckling. Supported by USPHS Grant HD 46949.