Two-step stimulation of intestinal Ca 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 Ca absorption during lactation by longterm 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 Ca absorption serves to provide Ca 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 Ca 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 Ca absorption rate to a new “baseline” (Step 1). During suckling, PRL surge further increased Ca absorption to a higher level (Step 2) in a nongenomic manner to match Ca loss in milk. PRL-enhanced apical Ca uptake was responsible for the increased transcellular transport, whereas PRL-enhanced paracellular transport required claudin-15, which regulated epithelial cation selectivity and paracellular Ca 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 Ca absorption resulted from long-term PRL exposure, which upregulated Ca transporter genes to elevate the transport baseline, and the suckling-induced transient PRL surge, which further increased Ca transport to the maximal capacity. The present findings also suggested that Ca supplementation at 15–30 min prior to breastfeeding may best benefit the lactating mother, since more Ca could be absorbed as a result of the suckling-induced PRL surge.