Two-step stimulation of intestinal Ca2+ absorption during lactation by long-term prolactin exposure and suckling-induced prolactin surge

Charoenphandhu N, Nakkrasae L, Kraidith K, Teerapornpuntakit J, Thongchote K, Thongon N, Krishnamra N. Two-step stimulation of intestinal Ca2+ absorption during lactation by long-term prolactin exposure and suckling-induced prolactin surge. Am J Physiol Endocrinol Metab 297: E609-E619, 2009. First published June 30, 2009; doi: 10.1152/ajpendo.00347.2009.-During 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-D-9k, 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.