Kurbel Sven, Radić Radivoje, Kotromanović Zeljko, Puseljić Zeljka, Kratofil Boris
Osijek Medical Faculty, Osijek, Croatia.
Med Hypotheses. 2003 Sep;61(3):346-50. doi: 10.1016/s0306-9877(03)00107-5.
Calcitriol is in plasma bound to transcalciferin and this results in a long calcitriol half-life in plasma (5-12h). Abundance of bound calcitriol molecules prevents the exact and quick control of its effects and makes it an inert regulator with a time lag between the changes of calcitriol synthesis and its effect on peripheral tissues. The added regulatory inertia is here defined as: calcitriol(bound)/calcitriol(free) and it approaches value of 99. Estrogens increase transcalciferin levels. It is possible that the estrogen-induced increase in the total calcitriol plasma pool makes calcitriol effects even more inert, augmenting and prolonging the calcitriol effects and thus improving calcium balance in women. Since calcitriol synthesis in kidneys depends on the PTH level, it can be assumed that the size of the total calcitriol pool in plasma reflects more the average PTH secretion during previous hours, than the high or low peaks of PTH secretion in the same period. In other words, one or more PTH tides of short duration are followed with a late calcitriol tide that lasts for hours, and even longer lasting rise in calcitriol effects. Bone integrity depends also on the cortisol level. A possible speculation is that the main result of all profound bone effect of hypecortisolemia, might be reduction of the bone amino acids uptake, thus allowing redistribution of available proteins. Both PTH and calcitriol prevent dangerous hypocalcemia. PTH is quick in mobilizing bone calcium, while calcitriol tends to increase absorption of dietary calcium. In case of low or no dietary calcium, calcitriol mobilizes bone calcium and thus increase PTH initiated demineralization. In the case of calcium abundance, increased plasma calcium reduces PTH levels. Calcitriol plasma level (reflecting previous PTH surges) can induce both calcium absorption and bone demineralization. This two-blade action is tuned by calcitonin that reduces osteoclastic bone resorption, allowing bone deposition of abundant calcium. An overnight fast with a reduced absorption of dietary calcium, might decrease plasma calcium below the regulatory set point, inducing an increase in PTH secretion. Increased average nighttime PTH secretion induces more calcitriol to be synthesized in kidneys. The resultant late calcitriol morning and daytime tide would stimulate calcium absorption from gut, or from bone, depending on the availability of dietary calcium. Due to the described time lag in calcitriol effects, increased calcium absorption might continue during daytime, regardless of the plasma calcium level. If plasma calcium is above the set point, calcitonin will allow excess calcium to deposit in bones. A speculation based on this model is that it might be more efficient to avoid calcium rich food for dinner or supper, and to administer calcium supplementation in the morning, during the calcitriol tide.
骨化三醇在血浆中与转钙蛋白结合，这导致其在血浆中的半衰期较长（5 - 12小时）。大量结合的骨化三醇分子阻碍了对其作用的精确快速控制，使其成为一种具有惰性的调节剂，在骨化三醇合成变化与其对外周组织的作用之间存在时间滞后。这里将增加的调节惰性定义为：骨化三醇（结合型）/骨化三醇（游离型），其接近99的值。雌激素会增加转钙蛋白水平。雌激素诱导的血浆中骨化三醇总量增加可能会使骨化三醇的作用更加惰性，增强并延长骨化三醇的作用，从而改善女性的钙平衡。由于肾脏中骨化三醇的合成取决于甲状旁腺激素（PTH）水平，可以推测血浆中骨化三醇总量的大小更多地反映了前几个小时的平均PTH分泌情况，而不是同一时期PTH分泌的高峰或低谷。换句话说，一个或多个持续时间短的PTH潮之后会跟着一个持续数小时甚至更持久的骨化三醇潮，以及骨化三醇作用的更持久升高。骨骼完整性也取决于皮质醇水平。一种可能的推测是，高皮质醇血症对骨骼所有深远影响的主要结果可能是减少骨骼对氨基酸的摄取，从而使可用蛋白质得以重新分布。PTH和骨化三醇都可预防危险的低钙血症。PTH能迅速动员骨钙，而骨化三醇则倾向于增加膳食钙的吸收。在膳食钙含量低或无膳食钙的情况下，骨化三醇会动员骨钙，从而增加PTH引发的脱矿作用。在钙含量丰富的情况下，血浆钙升高会降低PTH水平。血浆骨化三醇水平（反映先前的PTH激增）可诱导钙吸收和骨脱矿作用。这种双刃剑作用由降钙素调节，降钙素可减少破骨细胞的骨吸收，使丰富的钙得以沉积在骨骼中。夜间禁食且膳食钙吸收减少可能会使血浆钙降至调节设定点以下，从而诱导PTH分泌增加。夜间平均PTH分泌增加会促使肾脏合成更多的骨化三醇。由此产生的骨化三醇早晨和白天的潮会刺激肠道或骨骼对钙的吸收，这取决于膳食钙的可利用性。由于骨化三醇作用存在上述时间滞后现象，无论血浆钙水平如何，白天钙吸收可能会持续增加。如果血浆钙高于设定点，降钙素会使多余的钙沉积在骨骼中。基于此模型的一种推测是，晚餐或晚餐避免食用富含钙的食物，并在早晨骨化三醇潮期间补充钙可能会更有效。
