Two-step stimulation of intestinal Ca(2+) absorption during lactation by long-term prolactin exposure and suckling-induced prolactin surge.
During pregnancy and lactation, the enhanced intestinal Ca(2+) absorption serves to provide Ca(2+) 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(2+) 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 Ca(2+) absorption rate to a new "baseline" (Step 1). During suckling, PRL surge further increased Ca(2+) absorption to a higher level (Step 2) in a nongenomic manner to match Ca(2+) loss in milk. PRL-enhanced apical Ca(2+) uptake was responsible for the increased transcellular transport, whereas PRL-enhanced paracellular transport required claudin-15, which regulated epithelial cation selectivity and paracellular Ca(2+) 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(2+) absorption resulted from long-term PRL exposure, which upregulated Ca(2+) transporter genes to elevate the transport baseline, and the suckling-induced transient PRL surge, which further increased Ca(2+) transport to the maximal capacity. The present findings also suggested that Ca(2+) supplementation at 15-30 min prior to breastfeeding may best benefit the lactating mother, since more Ca(2+) could be absorbed as a result of the suckling-induced PRL surge.
Charoenphandhu
Narattaphol
N
Consortium for Calcium, Mahidol University, Bangkok, Thailand. naratt@narattsys.com
Nakkrasae
La-iad
LI
Kraidith
Kamonshanok
K
Teerapornpuntakit
Jarinthorn
J
Thongchote
Kanogwun
K
Thongon
Narongrit
N
Krishnamra
Nateetip
N
D000818:Animals; D000833:Animals, Suckling; D018938:Caco-2 Cells; D002118:Calcium / Q000378:metabolism*; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D007774:Lactation / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D011388:Prolactin / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013391:Sucking Behavior / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D011388:Prolactin; D002118:Calcium