Why do dairy cows sometime suffer from hypocalcemia after parturition?

分娩後の数日間は急激な泌乳開始に伴ってカルシウム（Ca）要求量が増加し，ほぼ全ての乳牛において血中カルシウム（Ca）濃度は低下する（低Ca血症）．この低下が著しい乳牛では，産褥麻痺（乳熱）と呼ばれる弛緩麻痺を特徴とする起立不能症候群を発症する．生体には低Ca血症に反応して骨のCa再吸収や腸管のCa吸収を増加させ，Caの恒常性を維持する機構が備わっている．しかし，分娩直後の乳牛では骨からのCa再吸収は抑制されるため，腸管からの吸収に強く依存している．乳牛では分娩前日に骨吸収抑制因子の一つであるエストロジェンの血中濃度が劇的に増加し，乳熱の発症リスクとして関与することが示唆されている．飼料中のCaは，受動輸送あるいは能動輸送によって粘膜上皮を通過し吸収される．Ca要求量が増加する妊娠や泌乳の期間中は，能動輸送が腸管上皮でのCa吸収の主流となる．Ca結合タンパクの一種であるcalbindin D9k（CaBP9k）は細胞質内でCaに結合し迅速 に拡散させる作用を有し，粘膜上皮におけるCaの能動輸送で重要な役割を果たしている．乳牛の消化 管においてCaBP9k mRNAは十二指腸に限局して発現することから，小腸近位部が粘膜上皮における能 動輸送の主要部位であると考えられる．このことは，乳牛の腸管におけるCa能動輸送がラット等の単 胃動物と比較して限局することを示している．CaBP9k mRNAの腸管発現量や血中の骨代謝マーカーならびに1,25-dihydroxyvitamin D3濃度は，牛の年齢とともに減少することが示され，加齢が乳牛の分娩性低Ca血症の重要な誘因の一つと考えられている.Most parturient cows experience varying degrees of hypocalcemia during the first several days after parturition while they adapt to the calcium（ Ca） demands of lactation. In some cases, the plasma Ca concentrations become too low to support nerve and muscle function, resulting in the clinical syndrome of parturient paresis（ milk fever）. Enhancement of bone Ca resorptive and intestinal Ca absorptive processes is the major homeostatic responses to hypocalcemia. However, it has been demonstrated that the Ca homeostasis of parturient cows depends only on intestinal Ca absorption soon after calving, because bone resorption is delayed for 1 week or more after parturition. Plasma concentrations of estrogen, a potent inhibitor of bone resorption, rise dramatically in the final days prior to parturition. Several studies have suggested that cows with higher plasma estrogen concentrations at parturition were at greater risk of developing milk fever. Dietary Ca can be absorbed from the intestinal lumen by passive diffusion between the epithelial cells （paracellular transport） and active transport across the epithelium （transepithelial transport）. Efficient intestinal Ca absorption occurs by transepithelial transport, when the Ca demand becomes greater during pregnancy and lactation. A Ca binding protein, calbindin D9k （CaBP9k） is one of the key factors playing an important role in the transepithelial Ca absorption, because it facilitates rapid diffusion of Ca across the cell. In dairy cattle, the highest transepithelial Ca transport activity is believed to occur in the proximal region of the small intestine, because detectable levels of mRNA coding for intestinal CaBP9k have been found to be localized only in the duodenum. It seems reasonable to believe that advancing age is an important predisposing factor of parturient hypocalcemia in dairy cows. Recent investigations have shown that the intestinal mRNA expression levels for CaBP9k and the plasma concentrations of bone resorption markers and 1,25-dihydroxyvitamin D3 decrease according to aging