Hypercalcaemia due to parathyroid hormone-related protein: long-term circulating levels may not reflect tumour activity

Papantoniou NE, Papapetrou PD, Antsaklis AJ, Kontoleon PE, Mesogitis SA, Aravantinos D. Circulating levels of immunoreactive parathyroid hormone-related protein and intact parathyroid hormone in human fetuses and newborns. Eur J Endocrinol 1996;134:437–42. ISSN 0804–4643 Undetectable or extremely low levels of circulating immunoreactive parathyroid hormone (PTH) have been reported in human newborns while PTH bioactivity was high. This prompted the hypothesis that the fetal calcemic hormone might be PTH-related protein. The purpose of this study was to measure circulating immunoreactive PTH-related protein in human fetuses and newborns in order to investigate this hypothesis. Parathyroid hormone-related protein (PTHrP(1–86)) and intact PTH were measured using two-site immunoradiometric assays in plasma obtained by cordocentesis from 23 fetuses (19–33 weeks of gestation), from 17 newborns at term (38–41 weeks), from their mothers and from 22 normal women of reproductive age. Plasma PTHrP was detectable in all but one of the fetuses and newborns and in all the mothers and the controls. The mean level was similar among fetuses (19–33 weeks) (0.43 ± 0.18 pmol/l), newborns (0.48 ±0.12), mothers (0.48 ±0.14) and normal controls (0.46 ± 0.09). Plasma PTH was found to be significantly higher in fetuses at midgestation (1.0 ± 0.99 pmol/l) than in the newborns (0.22 ± 0.21) (p < 0.0025); maternal PTH was significantly higher compared to fetal level at mid-gestation (2.1 ± 1.0, p < 0.01) as well as at term (2.69 ± 1.40, p < 0.001). In the control women PTH was 3.07 ± 1.25 pmol/l. These results showed that plasma amino-terminal PTHrP-(1–86)) is detectable during the second half of human fetal life and its level remains unchanged during this period of time, in contrast to changing levels of fetal plasma PTH. The relatively low PTHrP-(1–86) level that we found in the newborns is not responsible for the high PTH-like bioactivity found by some investigators in cord blood at term. Peter D Papapetrou, Second Division of Endocrinology, "Alexandra" Hospital, 80 Vas. Sofias & Lourou Streets, Athens 115 28, Greece

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Increased Potential of Bone Formation with the Intravenous Injection of a Parathyroid Hormone-Related Protein Minicircle DNA Vector

International Journal of Molecular Sciences ◽

10.3390/ijms22169069 ◽

2021 ◽

Vol 22 (16) ◽

pp. 9069

Author(s):

Jang-Woon Kim ◽

Narae Park ◽

Jaewoo Kang ◽

Yena Kim ◽

Hyerin Jung ◽

...

Keyword(s):

Parathyroid Hormone ◽

Bone Formation ◽

Bone Structure ◽

Human Mesenchymal Stem Cells ◽

Treated Group ◽

Related Protein ◽

Parathyroid Hormone Related Protein ◽

Alternative Delivery ◽

Minicircle Dna

Osteoporosis is commonly treated via the long-term usage of anti-osteoporotic agents; however, poor drug compliance and undesirable side effects limit their treatment efficacy. The parathyroid hormone-related protein (PTHrP) is essential for normal bone formation and remodeling; thus, may be used as an anti-osteoporotic agent. Here, we developed a platform for the delivery of a single peptide composed of two regions of the PTHrP protein (1–34 and 107–139); mcPTHrP 1–34+107–139 using a minicircle vector. We also transfected mcPTHrP 1–34+107–139 into human mesenchymal stem cells (MSCs) and generated Thru 1–34+107–139-producing engineered MSCs (eMSCs) as an alternative delivery system. Osteoporosis was induced in 12-week-old C57BL/6 female mice via ovariectomy. The ovariectomized (OVX) mice were then treated with the two systems; (1) mcPTHrP 1–34+107–139 was intravenously administered three times (once per week); (2) eMSCs were intraperitoneally administered twice (on weeks four and six). Compared with the control OVX mice, the mcPTHrP 1–34+107–139-treated group showed better trabecular bone structure quality, increased bone formation, and decreased bone resorption. Similar results were observed in the eMSCs-treated OVX mice. Altogether, these results provide experimental evidence to support the potential of delivering PTHrP 1–34+107–139 using the minicircle technology for the treatment of osteoporosis.

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