Reciprocity in the Developmental Regulation of Aquaporins 1, 3 and 5 during Pregnancy and Lactation in the Rat

Abstract

Milk secretion involves significant flux of water, driven largely by synthesis of lactose within the Golgi apparatus. It has not been determined whether this flux is simply a passive consequence of the osmotic potential between cytosol and Golgi, or whether it involves regulated flow. Aquaporins (AQPs) are membrane water channels that regulate water flux. AQP1, AQP3 and AQP5 have previously been detected in mammary tissue, but evidence of developmental regulation (altered expression according to the developmental and physiological state of the mammary gland) is lacking and their cellular/subcellular location is not well understood. In this paper we present evidence of developmental regulation of all three of these AQPs. Further, there was evidence of reciprocity since expression of the rather abundant AQP3 and less abundant AQP1 increased significantly from pregnancy into lactation, whereas expression of the least abundant AQP5 decreased. It would be tempting to suggest that AQP3 and AQP1 are involved in the secretion of water into milk. Paradoxically, however, it was AQP5 that demonstrated most evidence of expression located at the apical (secretory) membrane. The possibility is discussed that AQP5 is synthesized during pregnancy as a stable protein that functions to regulate water secretion during lactation. AQP3 was identified primarily at the basal and lateral membranes of the secretory cells, suggesting a possible involvement in regulated uptake of water and glycerol. AQP1 was identified primarily at the capillary and secretory cell cytoplasmic level and may again be more concerned with uptake and hence milk synthesis, rather than secretion. The fact that expression was developmentally regulated supports, but does not prove, a regulatory involvement of AQPs in water flux through the milk secretory cell.

Regulation and localization of vascular endothelial growth factor within the mammary glands during the transition from late gestation to lactation

“…Those authors found that AQP1 expression remained elevated from early to peak lactation, whereas we found that AQP1 expression in the MG decreased during this period. We also found that AQP3 expression remained elevated from day 2 to day 21 of lactation, whereas Nazemi et al [13] found that AQP3 expression decreased from early to peak lactation. Whether these differences reflect between-species or experimental divergence is unknown.…”

“…We also find that gene expression for AQP1 and 3, both of which are measures of vascular permeability [52], increases from late gestation to lactation. Nazemi et al [13] also recently reported that expression of AQP1 and 3 in the MG of rats increases between gestation and early lactation. Those authors found that AQP1 expression remained elevated from early to peak lactation, whereas we found that AQP1 expression in the MG decreased during this period.…”

“…As a result, increased abundance of hypoxia inducible factor-1α (HIF-1α) can upregulate VEGF-A expression [11,12]. Finally, sufficient vascular permeability within the MG is realized by the actions of developmentally-regulated [13], water-permeable aquaporins (AQP) that allow water to move from the microcirculation into milk [14]. Within the mammary glands, AQP1 localizes to the endothelium whereas AQP3 localizes to the epithelium to contribute to milk synthesis [15,16].…”

An Herbal Galactagogue Mixture Increases Milk Production and Aquaporin Protein Expression in the Mammary Glands of Lactating Rats

“…We also found that, in contrast to AQP-1 and AQP-3, which were predominantly expressed in cytoplasm, the subcellular localization of AQP-5 was exclusively present in nuclei in virgin rats whereas during lactation it was detected in both cytoplasm and nuclei. Nazemi et al also found that the immunohistochemical staining signals of AQP-5 were in mammary epithelial cells and duct system in rats but the signals were mainly in cytoplasm [ 23 ]. Both our study and the report by Nazemi et al show that the staining intensity of AQP-5 was lower than that of AQP-3 in lactating mammary glands.…”

“…In this study, immunohistochemical staining and western blot demonstrated that protein levels of AQP-3 and AQP-5 were significantly increased in lactating rats compared with virgin rats. Nazemi et al investigated the expression of AQP-1, AQP-3, and AQP-5 during pregnancy and lactation in rats and found that, compared with pregnancy stage, the mRNA levels of AQP-1 and AQP-3 were significantly increased at lactation stage [ 23 ]. Similar to the results in this study, they demonstrated significantly higher protein levels of AQP-3 at lactation than at pregnancy [ 23 ].…”