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

Abstract

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, ...

hPTH‐fragments (53–84) and (28–48) antagonize the stimulation of calcium release and repression of alkaline phosphatase activity by hPTH‐(1–34) in vitro

“…The data demonstrate that in combination, low concentrations of either fragment could abolish the effects of 10 nM PTH-(1-34) on calcium release and repression of ALP activity. This finding that different parts of the PTH molecule can exert opposing effects at widely differing concentrations suggests that distinct PTH-domains exert agonist and antagonist actions on bone tissue and are consistent with other findings, where low concentrations of PTH showed growth enhancing activities in avian [15,16] and in other cellular systems [17,18]. For determine a dose related response for both fragments a higher dilution may be required.…”

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

“…In the decades that followed the development of specific PTH assays, it was recognized that fetal blood contains high PTH-like bioactivity but low immunoreactive levels of PTH (3,20,21,67,571). PTHrP was cloned in 1987 (410,646,658), and subsequent work confirmed that it mimics many of the biological actions of PTH (333), circulates at high levels in fetal blood compared with PTH (168,306,600,671), and accounts for the high PTH-like bioactivity in fetal blood (7,94,396).…”

“…B) HUMAN DATA. As with animal fetuses, prior to the discovery of PTHrP it was recognized that human cord blood contained low immunoreactive intact PTH concentrations but high levels of PTH-like bioactivity as measured in cytochemical bioassays (20,21,571). The discrepancy is now explained by high circulating levels of PTHrP (600, 671), which mimics many of the actions of PTH on the PTH1R.…”

“…In human babies, PTH also circulates at low levels compared with the maternal circulation and normal adult values; very low (Ͻ0.5 pM) concentrations may be observed (20, 143, 168, 177, 255, 306, 501, 544, 571, 580, 598 -600, 671, 736). This suppression of PTH has been observed as early as 19 wk of gestation in preterm babies (501,571,580,599), although one study found unsuppressed PTH values in cord blood of infants aged 31-36 wk (152). The suppression of fetal PTH is considerable when it is realized that the maternal PTH value is also usually suppressed during pregnancy compared with normal adult values, at least in women from North America and Europe (328,339).…”

Parathyroid hormone-related peptide (PTHrP) regulates fetal–placental calcium transport through a receptor distinct from the PTH/PTHrP receptor

“…Furthermore, although 1,25-D (given at pharmacologic doses to the dam or fetus) can increase the fetal calcium content and blood level of calcium (7,8), fetuses of severely vitamin D-deficient, hypocalcemic rats have normal blood calcium levels and fully mineralized skeletons (9,10). Maternally derived PTH cannot cross the placenta (11), and fetal immunoreactive PTH levels are low throughout gestation in mammals (3,12).…”