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This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 297/3/E609    most recent 00347.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Charoenphandhu, N. Articles by Krishnamra, N. PubMed PubMed Citation Articles by Charoenphandhu, N. Articles by Krishnamra, N.

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

¹Consortium for Calcium and Bone Research; ²Department of Physiology, Faculty of Science, Mahidol University, Bangkok; and ³Department of Medical Science, Faculty of Science, Burapha University, Chonburi, Thailand

Submitted 27 May 2009 ; accepted in final form 26 June 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.

calcium transport; lactating rats; pituitary transplantation; pregnancy; small interfering RNA