Narattaphol CharoenphandhuLa Iad NakkrasaeKamonshanok KraidithJarinthorn TeerapornpuntakitKanogwun ThongchoteNarongrit ThongonNateetip KrishnamraMahidol UniversityBurapha University2018-09-132018-09-132009-09-01American Journal of Physiology - Endocrinology and Metabolism. Vol.297, No.3 (2009)15221555019318492-s2.0-69049119371https://repository.li.mahidol.ac.th/handle/20.500.14594/27147During pregnancy and lactation, the enhanced intestinal Ca2+absorption serves to provide Ca2+for fetal development and lactogenesis; however, the responsible hormone and its mechanisms remain elusive. We elucidated herein that prolactin (PRL) markedly stimulated the transcellular and paracellular Ca2+transport in the duodenum of pregnant and lactating rats as well as in Caco-2 monolayer in a two-step manner. Specifically, a long-term exposure to PRL in pregnancy and lactation induced an adaptation in duodenal cells at genomic levels by upregulating the expression of genes related to transcellular transport, e.g., TRPV5/6 and calbindin-D9k, and the paracellular transport, e.g., claudin-3, thereby raising Ca2+absorption rate to a new "baseline" (Step 1). During suckling, PRL surge further increased Ca2+absorption to a higher level (Step 2) in a nongenomic manner to match Ca2+loss in milk. PRL-enhanced apical Ca2+uptake was responsible for the increased transcellular transport, whereas PRL-enhanced paracellular transport required claudin-15, which regulated epithelial cation selectivity and paracellular Ca2+movement. Such nongenomic PRL actions were mediated by phosphoinositide 3-kinase, protein kinase C, and RhoA-associated coiled-coil-forming kinase pathways. In conclusion, two-step stimulation of intestinal Ca2+absorption resulted from long-term PRL exposure, which upregulated Ca2+transporter genes to elevate the transport baseline, and the suckling-induced transient PRL surge, which further increased Ca2+transport to the maximal capacity. The present findings also suggested that Ca2+supplementation at 15-30 min prior to breastfeeding may best benefit the lactating mother, since more Ca2+could be absorbed as a result of the suckling-induced PRL surge. Copyright © 2009 the American Physiological Society.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyMedicineArticleSCOPUS10.1152/ajpendo.00347.2009