Ablation of calcitonin/calcitonin gene-related peptide-alpha impairs fetal magnesium but not calcium homeostasis.
We used the calcitonin/calcitonin gene-related peptide (CGRP)-alpha gene knockout model (Ct/Cgrp null) to determine whether calcitonin and CGRPalpha are required for normal fetal mineral homeostasis and placental calcium transfer. Heterozygous (Ct/Cgrp(+/-)) and Ct/Cgrp null females were mated to Ct/Cgrp(+/-) males. One or two days before term, blood was collected from mothers and fetuses and analyzed for ionized Ca, Mg, P, parathyroid hormone (PTH), and calcitonin. Amniotic fluid was collected for Ca, Mg, and P. To quantify skeletal mineral content, fetuses were reduced to ash, dissolved in nitric acid, and analyzed by atomic absorption spectroscopy for total Ca and Mg. Placental transfer of (45)Ca at 5 min was assessed. Ct/Cgrp null mothers had significantly fewer viable fetuses in utero compared with Ct/Cgrp(+/-) and wild-type mothers. Fetal serum Ca, P, and PTH did not differ by genotype, but serum Mg was significantly reduced in null fetuses. Placental transfer of (45)Ca at 5 min was normal. The calcium content of the fetal skeleton was normal; however, total Mg content was reduced in Ct/Cgrp null skeletons obtained from Ct/Cgrp null mothers. In summary, maternal absence of calcitonin and CGRPalpha reduced the number of viable fetuses. Fetal absence of calcitonin and CGRPalpha selectively reduced serum and skeletal magnesium content but did not alter ionized calcium, placental calcium transfer, and skeletal calcium content. These findings indicate that calcitonin and CGRPalpha are not needed for normal fetal calcium metabolism but may regulate aspects of fetal Mg metabolism.
McDonald
Kirsten R
KR
Faculty of Medicine-Endocrinology, Memorial University of Newfoundland, St. John's, Canada.
Fudge
Neva J
NJ
Woodrow
Janine P
JP
Friel
James K
JK
Hoff
Ana O
AO
Gagel
Robert F
RF
Kovacs
Christopher S
CS
D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D002116:Calcitonin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002118:Calcium / Q000097:blood / Q000378:metabolism*; D005314:Embryonic and Fetal Development / Q000502:physiology; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005333:Fetus / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006132:Growth Plate / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D008098:Litter Size / Q000235:genetics / Q000502:physiology; D008274:Magnesium / Q000097:blood / Q000378:metabolism*; D008297:Male; D008431:Maternal-Fetal Exchange / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010920:Placenta / Q000378:metabolism; D010929:Placentation; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis
D012333:RNA, Messenger; D002116:Calcitonin; D008274:Magnesium; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium