The role of parathyroid hormone‐related protein in calcium homeostasis in the fetal pig

Abbas, S. K.; Ratcliffe, W. A.; Moniz, C.; Dixit, Mehul; Caple, I. W.; Silver, M.; Fowden, AL; Care, A. D.

doi:10.1113/expphysiol.1994.sp003785

Cited by 16 publications

(8 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cytochemical assays have revealed that fetal blood contains high PTH-like bioactivity, which cannot be accounted for by the low immunoreactive levels of PTH (3,20,67). Following the discovery of PTHrP and the development of specific radioimmunoassays for it, studies in fetal pigs (7) and sheep (94,396) determined that high immunoreactive levels of PTHrP correlated closely with, and likely accounted for, the high PTH-like bioactivity in fetal blood.…”

Section: Pthrpmentioning

confidence: 99%

“…Venous umbilical PTHrP levels are higher than umbilical arterial levels in pigs, which suggests that the placenta may be an important source of circulating PTHrP in the fetus (7). As discussed in section IIC, the fetal parathyroids were originally proposed to be the source of PTHrP in fetal sheep, but the effect of fetal parathyroidectomy on the plasma PTHrP concentration was not reported.…”

Section: Pthrpmentioning

confidence: 99%

“…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). The relative difference in circulating levels of PTHrP and PTH may even be underestimated because the commonly used PTHrP 1-86 assay does not detect biologically active PTHrP .…”

Section: Parathyroid Hormone-related Proteinmentioning

confidence: 99%

See 2 more Smart Citations

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

Kovacs

2014

Physiological Reviews

207

188

View full text Add to dashboard Cite

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.

show abstract

Section: Pthrpmentioning

confidence: 99%

Section: Pthrpmentioning

confidence: 99%

Section: Parathyroid Hormone-related Proteinmentioning

confidence: 99%

See 1 more Smart Citation

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

Kovacs

2014

Physiological Reviews

207

188

View full text Add to dashboard Cite

show abstract

“…In most tissues in which PTHrp is expressed, target cells for PTHrp were found adjacent. They often respond to PTHrp by an activation of adenylate cyclase (AC) and subsequently protein kinases A (PKA) (2,3), but this is not a general rule. In fact, keratinocytes have been shown to respond to the PTHrp they produce and secrete, by a yet uncharacterized receptor, which uses calcium ions as a second messenger and thus is associated to the protein kinase C (PKC) pathway (4).…”

Section: Introductionmentioning

confidence: 99%

Effect of parathyroid hormone‐related protein on fibroblast proliferation and collagen metabolism in human skin

Maioli¹,

Fortino²,

Torricelli³

et al. 2002

Experimental Dermatology

View full text Add to dashboard Cite

The parathyroid hormone-related protein (PTHrp), structurally similar to the parathyroid hormone (PTH) in its NH(2)-terminal part, was first identified as a tumour-derived peptide responsible for a paraneoplastic syndrome known as humoral hypercalcemia of malignancy. The PTHrp gene is expressed not only in cancer but also in normal tissues during adult and/or fetal life, where it plays predominantly paracrine and/or autocrine roles. In the skin PTHrp produced by keratinocytes acts on fibroblasts by complex cooperative circuits involving cytokines and growth factors. In this report, we studied the direct effects of synthetic PTHrp 1-40 on proliferation and collagen synthesis and matrix metalloproteinase-2 (MMP-2) activity in cultures of fibroblasts isolated from normal human skin. Fibroblasts exposure to varying doses of PTHrp for 48 h, significantly and dose-dependently inhibited proliferation evaluated by [(3)H]-thymidine incorporation into DNA. A dose-dependent stimulation of cAMP released into the medium was concomitantly observed. In contrast, PTHrp had no effect on collagen synthesis evaluated either by [(3)H]-proline incorporation or by radioimmunoassay (RIA) of the carboxyterminal fragment of type I procollagen (PICP). MMP-2 activity, evaluated by quantitative zymographic analysis, was significantly increased by PTHrp treatment at doses of 160 and 320 nM. These findings indicate that PTHrp may play a role in normal dermal physiology by controlling both fibroblast proliferation and extracellular matrix degradation.

show abstract

“…Numerous studies have demonstrated that a recombined PTHrP induces hypercalcaemia and bone resorption, stimulates phosphate transport and augments cAMP synthesis in kidneys and in bone cells [32]. The fragment 67-86 stimulates transport of calcium ions across the placenta from the mother to her foetus [1]. The fragment 67-86 stimulates transport of calcium ions across the placenta from the mother to her foetus [1].…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of immunocytochemical determination of parathyroid hormone-related peptide expression in cells of mammary ductal carcinoma. Analysis of 7 years of the disease course

et al. 2003

View full text Add to dashboard Cite

Parathyroid hormone-related peptide (PTHrP) participates in the development of humoral hypercalcaemia of malignancy. The peptide is thought to affect growth and differentiation of normal and neoplastic cells. The present study aimed at evaluation of the relationship between survival time and development of distant metastases in patients with ductal mammary carcinoma on the one hand and PTHrP expression on the other. Immunocytochemical reactions using mouse monoclonal (clone 212-10.7) anti-PTHrP (38-64) antibodies were performed in paraffin sections originating from 47 patients with ductal mammary carcinoma. Expression of the protein was quantified employing a scale, considering the number of positive cells and intensity of the reaction (immunoreactive score, IRS). Survival time of the patients, determined during the course of a 7-year observation was also analysed. The obtained results demonstrated a relationship between intensity of PTHrP expression and the survival time. Patients with high expression of PTHrP (IRS>6) manifested longer survival than patients with lower PTHrP expression (IRS≤6; Cox'es F test, P<0.05). Moreover, in the group with the lower PTHrP expression, a negative relationship was detected between expression of the protein and the survival time (Cox'es model, P<0.05). No relationship was detected between PTHrP expression and the development of distant metastases.

show abstract

The role of parathyroid hormone‐related protein in calcium homeostasis in the fetal pig

Cited by 16 publications

References 11 publications

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

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

Effect of parathyroid hormone‐related protein on fibroblast proliferation and collagen metabolism in human skin

Prognostic value of immunocytochemical determination of parathyroid hormone-related peptide expression in cells of mammary ductal carcinoma. Analysis of 7 years of the disease course

Contact Info

Product

Resources

About