Expression of Messenger Ribonucleic Acids Encoding a Parathyroid Hormone-Like Peptide in Normal Human and Animal Tissues with Abnormal Expression in Human Parathyroid Adenomas

Weir, Eleanor C.; Mangin, Marguerite; Dannies, Priscilla S.; Kinder, Barbara K.; Deftos, Leonard J.; Brown, Edward M.; Broadus, Arthur E.

doi:10.1210/mend-2-12-1230

Cited by 208 publications

(75 citation statements)

References 33 publications

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“…Several fetal tissues in different species can synthesize PTHrP, including parathyroid, placental membranes (45,46), and liver (47). Suggestively, human fetuses and patients with humoral hypercalcemia of malignancy do share certain biochemical features, viz.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

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

et al. 1991

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“…Although originally discovered in a variety of malignancies, mRNA encoding PLP has been identified in both normal and adenomatous tissue of several species. This includes normal human keratinocytes, stomach, normal islet cell, lactating mammary glands, normal and adenomatous parathyroid glands, brain, and fetal liver (20)(21)(22). In addition, cultured human keratinocytes secrete a material which stimulates adenylate cyclase activity in osteosarcoma cells (23) and may therefore represent a biologically active form of PLP.…”

Section: Introductionmentioning

confidence: 99%

Regulation of parathyroid hormone-like peptide in cultured normal human keratinocytes. Effect of growth factors and 1,25 dihydroxyvitamin D3 on gene expression and secretion.

Kremer¹,

Karaplis²,

Henderson³

et al. 1991

J. Clin. Invest.

125

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“…The PTHrP cDNA encodes the 141-amino-acid isoform of PTHrP and was obtained from EcoRI-restricted pBRF5O [4]. After prehybridization at 42"C, the filters were hybridized according to [19], with modifications in the hybridization (65 "C) and washing (70°C) temperatures. The filters were exposed to Amersham Hyperfilm for the times indicated in the figure legends.…”

Section: Rna Preparations and Northern Analysismentioning

confidence: 99%

Synthesis of human parathyroid‐hormone‐related protein(1–141) in Saccharomyces cerevisiae

Rian

Jemtland

Olstad

et al. 1993

European Journal of Biochemistry

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Gene fusions have been widely used in heterologous expression systems as a technique to stabilize the recombinant product against proteolysis, increase the translational initiation efficiency or to serve as an affinity handle for the purification of the protein. A further advantage is the potential to generate an authentic amino terminus of the foreign protein when this is vital for its biological activity, such as for the ability of human parathyroid-hormone-related protein (hPTHrP) to mediate activation of adenylate cyclase. We report here the construction and utility of a ubiquitin fusion protein system for production of the otherwise short-lived hPTHrP(1-141) as a carboxyl extension to ubiquitin in yeast. A hybrid gene containing the hFTHrP(1-141) cDNA coding region fused in-frame to the 3' end of the yeast ubiquitin cDNA was constructed and expressed under the control of the regulatable yeast metallothionein promoter. The recombinant protein was purified to homogeneity and finally characterized by N-terminal amino acid sequencing and amino acid composition analysis, demonstrating that the fusion protein was cleaved correctly and quantitatively in vivo by an ubiquitin-specific yeast endoprotease to generate authentic hPTHrP(1-141). hPTHrP(1-141) stimulated adenylate cyclase in rat osteosarcoma cell membranes to the same extent as equimolar amounts of recombinant human parathyroid hormone( 1 -84) and [TyP4]hPTHrP( 1 -34)amide. Thus, this expression cloning strategy permits the production of authentic, biologically active recombinant hPTHrP(1-141), and the procedure can easily be adapted to make PTHrP analogues for further studies of its domain-specific activities and biological roles.The parathyroid-hormone-related protein (PTHrP) gene is expressed in a wide range of both malignant and normal tissues. PTHrP is known as a factor causing humoral hypercalcemia of malignancy and has recently been implicated in several conditions of normal physiology (reviewed in [l]).The parathyroid-hormone-like effects of PTHrP are localized to the amino acid residues 1-34 [2, 31; residues 1-13 show a 70% similarity to parathyroid hormone [41. Because of this, PTHrP mimics some of the effects of PTH in bone and kidney, where the two hormones share the same receptor [ 5 ] , the most characteristic being mediated via activation of adenylate cyclase. The presence of the first two amino acids at the amino terminus, and partly also their identity, is vital for this action [6]. Binding to the FTW PTHrP receptor, however, appears to be confined within residues 14-34 [7], yet this region is divergent from the corresponding region in PTH. In addition, synthetic mid-region and carboxyl-terminal subfragments of PTHrP are shown to have separate effects which are probably not mediated via Abbreviations. PTHrP, parathyroid-hormone-related protein; PTH, parathyroid hormone; h, human; PCR, polymerase chain reaction.binding to the recently cloned PTH/PTHrP receptor [8, 91. It is also conceivable that these subfragments have their normal counterp...

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Expression of Messenger Ribonucleic Acids Encoding a Parathyroid Hormone-Like Peptide in Normal Human and Animal Tissues with Abnormal Expression in Human Parathyroid Adenomas

Cited by 208 publications

References 33 publications

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

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

Regulation of parathyroid hormone-like peptide in cultured normal human keratinocytes. Effect of growth factors and 1,25 dihydroxyvitamin D3 on gene expression and secretion.

Synthesis of human parathyroid‐hormone‐related protein(1–141) in Saccharomyces cerevisiae

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