Parathormone and Perinatal Calcium Homeostasis

Schedewie, H; Odell, William D.; Fisher, Delbert A.; Krutzik, Siegfried; Dodge, Michael; Cousins, Larry; Fiser, William P.

doi:10.1203/00006450-197901000-00001

Cited by 55 publications

(26 citation statements)

References 22 publications

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“…This hypothesis warrants further investigation once the molecular identity of the renal magnesium transporters has been described. The serum PTH concentration of 8-wk-old OD was lower than that of OC rats in the current study, which is in accordance with observations in human neonates (2,19,20). A number of hypotheses have been proposed to account for the apparent paradox of hypocalcemia and low PTH concentration.…”

Section: Discussionsupporting

confidence: 80%

“…We assessed renal function in rats at 4 wk of age, before puberty, and at 8 wk of age, after puberty, to determine whether in utero exposure to maternal diabetes exerts a long-term programming effect on offspring kidney function. We also measured serum PTH concentration, as this has been reported to be lower in human offspring of diabetic pregnancy (2,19,20) and may contribute to altered renal calcium and magnesium handling.…”

mentioning

confidence: 99%

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Increased Renal Tubular Reabsorption of Calcium and Magnesium by the Offspring of Diabetic Rat Pregnancy

et al. 2005

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Diabetic pregnancy has a marked influence on offspring calcium and magnesium homeostasis. Urinary excretion of calcium and magnesium is reduced, yet offspring of diabetic pregnancy exhibit hypomagnesemia and hypocalcemia. The aim of this study was to measure renal hemodynamic and tubular function in the offspring of diabetic (OD) and control, nondiabetic (OC) rats at 4 and 8 wk of age to determine the glomerular and tubular mechanisms through which renal calcium and magnesium handling are programmed in utero. The fraction of filtered calcium that was excreted was significantly lower in OD at both 4 and 8 wk of age [8 wk: OC (n ϭ 6), 11.8 Ϯ 2.9 versus OD (n ϭ 5), 4.3 Ϯ 0.6%; p Ͻ 0.05] and that of magnesium was lower at 8 wk of age [OC (n ϭ 6), 42.4 Ϯ 7.5 versus OD (n ϭ 5), 13.0 Ϯ 1.7%; p Ͻ 0.01]. This increased reabsorption occurred despite an elevated GFR in OD. These findings clearly indicate that tubular reabsorptive mechanisms for calcium and magnesium are increased markedly in OD. Serum PTH concentration was reduced in 8-wk-old OD [OC (n ϭ 7), 539.4 Ϯ 142.1 versus OD (n ϭ 9), 174.3 Ϯ 69.4 pg/ml; p Ͻ 0.05], consistent with previous reports in human infants. Taken together, these observations suggest that the basis for the altered renal magnesium and calcium handling in OD involves increased tubular transport activity and possibly increased sensitivity of these mechanisms to PTH. Diabetic pregnancy has a marked impact on maternal calcium and magnesium homeostasis in both humans and rats. Hypomagnesemia has been widely reported in human diabetic pregnancy (1-3), and diabetic pregnant rats display a marked increase in urinary magnesium excretion (4,5). A reduction in third-trimester plasma calcium concentration has been observed in human diabetic pregnancy in one study (3), but the majority of studies have found no difference in calcium concentrations between normal and diabetic pregnancies. However, in the diabetic rat, pregnancy is associated with marked increases in urinary calcium (4,5) and hypocalcemia in some (4) but not all studies (6).These changes in maternal divalent ion handling have a profound impact on the developing fetus. Human offspring of diabetic pregnancy exhibit hypomagnesemia and hypocalcemia as neonates (2,7-9). In the rat, renal handling of calcium and magnesium is also altered in the offspring of streptozotocin (STZ)-treated diabetic rats (OD). We recently reported that OD retain both calcium and magnesium as neonates and that this continues into adulthood (10). These changes in divalent ion homeostasis also occur in conjunction with changes in bone structure. Human offspring of diabetic pregnancy are susceptible to congenital malformations, including skeletal abnormalities (11), and have lower bone mineral content (12). Reduced bone mineral content and abnormal skeletal development have also been observed in the offspring of STZ-treated diabetic rat mothers (13,14). We recently extended these observations and showed that offspring of STZ-treated diabetic rats have reduced trabecular and ...

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Section: Discussionsupporting

confidence: 80%

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confidence: 99%

Increased Renal Tubular Reabsorption of Calcium and Magnesium by the Offspring of Diabetic Rat Pregnancy

et al. 2005

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“…Human fetuses share the finding of an elevated serum calcium and ionized calcium, typically 0.30 -0.50 mM above the maternal level (143,148,463,523,594,595). This has been demonstrated at 15-20 wk of gestation by fetoscopy (453), and at delivery of preterm singleton and twin pregnancies (mean gestational age 33 wk) (152).…”

Section: Human Datamentioning

confidence: 99%

Bone Development and Mineral Homeostasis in the Fetus and Neonate: Roles of the Calciotropic and Phosphotropic Hormones

Kovacs

2014

Physiological Reviews

208

188

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Mineral and bone metabolism are regulated differently in utero compared with the adult. The fetal kidneys, intestines, and skeleton are not dominant sources of mineral supply for the fetus. Instead, the placenta meets the fetal need for mineral by actively transporting calcium, phosphorus, and magnesium from the maternal circulation. These minerals are maintained in the fetal circulation at higher concentrations than in the mother and normal adult, and such high levels appear necessary for the developing skeleton to accrete a normal amount of mineral by term. Parathyroid hormone (PTH) and calcitriol circulate at low concentrations in the fetal circulation. Fetal bone development and the regulation of serum minerals are critically dependent on PTH and PTH-related protein, but not vitamin D/calcitriol, fibroblast growth factor-23, calcitonin, or the sex steroids. After birth, the serum calcium falls and phosphorus rises before gradually reaching adult values over the subsequent 24 -48 h. The intestines are the main source of mineral for the neonate, while the kidneys reabsorb mineral, and bone turnover contributes mineral to the circulation. This switch in the regulation of mineral homeostasis is triggered by loss of the placenta and a postnatal fall in serum calcium, and is followed in sequence by a rise in PTH and then an increase in calcitriol. Intestinal calcium absorption is initially a passive process facilitated by lactose, but later becomes active and calcitriol-dependent. However, calcitriol's role can be bypassed by increasing the calcium content of the diet, or by parenteral administration of calcium.

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“…Moreover, biologically active PTH circulates in normal subjects at picomolar concentrations (6, 7), which, until recently, have been beyond the detectability of most assay systems. It is not surprising, then, that iPTH in fetal and umbilical cord blood has been reported as indeterminate or low in some series (5,(8)(9)(10)(11)(12)(13)(14) and normal, or even elevated, compared with maternal or other adult levels (4, 15-18) in others. A variety of iPTH levels have also been reported in association with early neonatal hypocalcemia (1, 3,12,19).…”

mentioning

confidence: 99%

“…It is not surprising, then, that iPTH in fetal and umbilical cord blood has been reported as indeterminate or low in some series (5,(8)(9)(10)(11)(12)(13)(14) and normal, or even elevated, compared with maternal or other adult levels (4, 15-18) in others. A variety of iPTH levels have also been reported in association with early neonatal hypocalcemia (1, 3,12,19).Using the ultrasensitive CBA for PTH developed by Chambers (20), Care et al (21,22) showed that bioPTH in porcine fetal plasma exceeds paired maternal plasma bioPTH. Similarly, Allgrove et al (14) reported that human term umbilical cord plasma bioPTH is elevated 5-to 6-fold above paired maternal plasma bioPTH and significantly exceeds values determined in normocalcemic adults.…”

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confidence: 99%

Circulating Levels of Biologically Active and Immunoreactive Intact Parathyroid Hormone in Human Newborns

et al. 1991

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ABSTRACT. We evaluated circulating levels of biologically active and immunoreactive intact parathyroid hormone in 47 newborns at birth and eight hypocalcemic preterm infants during the first 10 d of life. Use of two sensitive detection systems, the cytochemical bioassay and an immunoradiometric assay specific for intact parathyroid hormone, enabled us to compare plasma concentrations of PTH-like bioactivity (bioPTH) and iPTH-(1-84). Mean umbilical venous plasma bioPTH was elevated in nondiabetic term and preterm newborns [22.5 + 3.1 (fSEM) and 15.8 f 2.5 ng-equiv/L, respectively] compared with normal adult subjects (9.8 2 2.6 ng-equiv/ L; p < 0.01). Umbilical bioPTH was suppressed in five term infants of diabetic mothers (2.6 f 0.4 ng-equiv/L). In contrast, iPTH-(1-84) was low in term and preterm nondiabetic infants' and term infants of diabetic mothers' umbilical samples (5.4 f 1.5, 4.3 ' . 1.5, and 2.4 + 1.0 ng/ L, respectively). Umbilical venous bioPTH was highly correlated with the magnitude of the transplacental calcium gradient (r = 0.90; p < 0.05). In eight preterm infants studied longitudinally, by 24-36 h of life, declining plasma total and ionized calcium (1.71 f 0.04 and 0.78 f 0.03 mmol/L, respectively) were accompanied by a significant rise in both bioPTH (41.2 f 6.3 ng-equiv/L) and iPTH-(1-84) (56.3 f 11.6 ng/L). These data indicate that the 3rd trimester fetoplacental circulation contains levels of bioPTH several-fold higher than those of immunoreactive intact hormone. We also conclude that even hypocalcemic preterm newborn infants can significantly elevate circulating levels of FTH. (Pediatr Res 29: 201-207,1991) Abbreviations PTH, parathyroid hormone iPTH-(1-84), immunoreactive intact parathyroid hormone bioPTH, parathyroid hormone-like biologic activity IDM, infant of a diabetic mother Can total calcium concentration Ca,, ionized calcium concentration CBA, cytochemical bioassay G6PD, glucose 6-phosphate dehydrogenase DCT, distal convoluted tubule PTHrP, parathyroid hormone-related peptide Received June 14, 1990; accepted October 2, 1990. In humans and other mammals, the extracellular total and ionized calcium concentrations change dynamically during the transition from fetal to extrauterine life. The fetal circulation of mammals in the 3rd trimester is hypercalcemic relative to that of the mother. In humans, cessation of transplacental flow of calcium at birth is associated with decrements in CaT and Ca, concentrations. Blood calcium stabilizes I to 2 d after birth, then rises progressively to levels observed in older children and adults. An exaggeration of this sequence of events, early neonatal hypocalcemia (CaT < 1.75 mmol/L; <7.0 mg/dL), occurs in at least 35 to 50% of preterm newborn infants ( l , 2 ) and more than 90% of extremely preterm infants (3).Inference from other hypercalcemic states has suggested that the chronic hypercalcemia of late fetal existence might suppress fetal PTH secretion (4) and that neonatal parathyroid suppression might persist for several days postpartum, ...

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Parathormone and Perinatal Calcium Homeostasis

Cited by 55 publications

References 22 publications

Increased Renal Tubular Reabsorption of Calcium and Magnesium by the Offspring of Diabetic Rat Pregnancy

Increased Renal Tubular Reabsorption of Calcium and Magnesium by the Offspring of Diabetic Rat Pregnancy

Bone Development and Mineral Homeostasis in the Fetus and Neonate: Roles of the Calciotropic and Phosphotropic Hormones

Circulating Levels of Biologically Active and Immunoreactive Intact Parathyroid Hormone in Human Newborns

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