tailieunhanh - Biochemical, Genetic, and Molecular Interactions in Development - part 8

Quy định canxi máu thai nhi. , Bình thường, cao cấp canxi của thai nhi, mà phụ thuộc vào PTHrP, kích hoạt các CaSR tuyến cận giáp, và PTH là bị đàn áp. B, Trong trường hợp không có PTHrP, mức độ canxi thai nhi rơi xuống một mức mà bây giờ là thiết lập bởi các CaSR tuyến cận giáp | Fetal Mineral Homeostasis 297 Fig. 1. Fetal blood calcium regulation. A Normal high fetal calcium level which is dependent on PTHrP activates the parathyroid CaSR and PTH is suppressed. B In the absence of PTHrP the fetal calcium level falls to a level that is now set by the parathyroid CaSR PTH is stimulated to maintain the ionized calcium at the normal adult level maternal . Reproduced with permission from ref. 1. had a greater impact on the fetal blood calcium than lack of PTHrP the combined loss of both PTH and PTHrP resulted in the lowest blood calcium level a level that is equal to that observed in fetal mice lacking the PTH PTHrP receptor Pthr1 -null fetuses in the same genetic background. Fetal parathyroids also are required for normal regulation of serum magnesium and phosphate concentrations as observed in thyroparathyroidectomized fetal lambs that had a reduced serum magnesium concentration 26 and an increase in the serum phosphate level 27 . Similarly absence of PTH and parathyroids in Hoxa3-null fetuses also causes hypomagnesemia and hyperphosphatemia 4 . Absence of PTHrP alone causes hyperphosphatemia but the serum magnesium concentration is unaltered unpublished data ref. 4 . Although a Pth-null model has now been published the effects of lack of PTH on fetal calcium phosphate or magnesium concentrations has not been reported 28 . As discussed see section titled Fetal Regulation there is consistent evidence that PTHrP regulates placental calcium transfer but conflicting evidence between sheep and mouse models that parathyroids are required for this process or that parathyroids make PTHrP. A detailed examination of normal fetal rat parathyroids found no detectable PTHrP mRNA by in situ hybridization or rt-PCR and no detectable PTHrP by immunohistochemistry 29 . The fetal parathyroids are required for normal accretion of mineral by the fetal skeleton as discussed in section entitled Fetal Skeleton. CALCIUM-SENSING RECEPTOR Postnatally the CaSR sets the