The expression of parathyroid hormone-related protein mRNA and immunoreactive protein in human amnion and choriodecidua is increased at term compared with preterm gestation

Abstract Parathyroid hormone-related protein (PTHrP) gene expression and/or immunoreactive protein have previously been identified in the uterus and intrauterine gestational tissues. The putative roles of PTHrP during pregnancy include vasodilatation, regulation of placental calcium transfer, uterine smooth muscle relaxation and normal fetal development. The aims of this study were 1) to determine the tissue-specific and temporal expression of PTHrP mRNA and immunoreactive protein in human gestational tissues collected at preterm and term; and 2) to determine the effect of labour on PTHrP expression by collecting these tissues from women undergoing elective caesarean section (before labour), intra-partum caesarean section during spontaneous-onset labour (during labour), and women with spontaneous labour and normal vaginal delivery (after labour). Total RNA and protein were extracted from placenta, amnion (over placenta and reflected) and choriodecidua for analysis by Northern blot (using a specific human PTHrP cDNA probe), and by N-terminal PTHrP RIA respectively. In amnion over placenta, reflected amnion and choriodecidua both PTHrP mRNA relative abundance and immunoreactive protein were significantly elevated at term compared with preterm (P<0·01). At term, both PTHrP and its mRNA were significantly greater in amnion than in placenta and choriodecidua (P<0·05). Also, both PTHrP and its mRNA were significantly elevated in amnion over placenta compared with reflected amnion (P<0·05). The expression of PTHrP and its mRNA did not change in association with term labour or rupture of the fetal membranes, therefore this study provides no evidence for a specific PTHrP role in the onset and/or maintenance of term labour. However, the significant up-regulation of PTHrP mRNA and protein in the fetal membranes at term compared with preterm suggests an important role in late human pregnancy. Journal of Endocrinology (1997) 154, 103–112

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Parathyroid hormone-related protein(1-34) in gestational fluids and release from human gestational tissues

Journal of Endocrinology ◽

10.1677/joe.0.1650657 ◽

2000 ◽

Vol 165 (3) ◽

pp. 657-662 ◽

Cited By ~ 18

Author(s):

W Farrugia ◽

PW Ho ◽

GE Rice ◽

JM Moseley ◽

M Permezel ◽

...

Keyword(s):

Parathyroid Hormone ◽

Amniotic Fluid ◽

G Protein ◽

Calcium Transport ◽

Fetal Membranes ◽

Related Protein ◽

Parathyroid Hormone Related Protein ◽

Gestational Tissues ◽

Epithelial Growth ◽

Stimulation Of

Parathyroid hormone-related protein (PTHrP) is present in fetal and gestational tissues, in which its proposed roles include stimulation of epithelial growth and differentiation, vasodilatation of the uteroplacental vasculature, relaxation of uterine muscle and stimulation of placental calcium transport. The aim of this study was to determine whether the release of PTHrP from gestational tissue explants was tissue specific. In addition, PTHrP concentrations were measured in maternal plasma, umbilical artery and vein plasma, and amniotic fluid from term, uncomplicated pregnancies before the onset of labour. PTHrP was detected in low concentrations in the mother, fetus and placental tissue. Amniotic fluid had ten times the PTHrP concentration compared with that in the maternal or fetal circulations. Using late pregnant human gestational tissues in an in vitro explant system, we found that amnion over placenta, choriodecidua, reflected amnion, and placenta released PTHrP into culture medium in progressively greater amounts over 24 h (P<0.05). This release was not associated with a loss of cell membrane integrity, as indicated by measurement of the intracellular enzyme, lactate dehydrogenase, in the incubation media. After 24 h incubation, the fetal membranes released significantly (P<0.05) greater amounts of PTHrP than did the placenta (placenta 3. 7+/-0.5 pmol PTHrP/g protein). Amnion over placenta released significantly more PTHrP (139.3+/- 43.1 pmol PTHrP/g protein) than did reflected amnion (29.0+/-8.3 pmol PTHrP/g protein) (P<0.05). This study unequivocally demonstrated that human gestational tissues release PTHrP and it was concluded that the main contributors to PTHrP in amniotic fluid were the human fetal membranes, particularly amnion over placenta. Fetal membrane-derived and amniotic fluid PTHrP are proposed to have stimulatory effects on epithelial growth and differentiation in fetal lung, gut, skin and hair follicles and paracrine effects on placental vascular tone and calcium transport.

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Parathyroid hormone-related protein in human term placenta and membranes

Journal of Endocrinology ◽

10.1677/joe.0.1420217 ◽

1994 ◽

Vol 142 (2) ◽

pp. 217-224 ◽

Cited By ~ 37

Author(s):

S J Bowden ◽

J F Emly ◽

S V Hughes ◽

G Powell ◽

A Ahmed ◽

...

Keyword(s):

Parathyroid Hormone ◽

Caesarean Section ◽

Amniotic Fluid ◽

Elective Caesarean Section ◽

Molecular Forms ◽

Molecular Heterogeneity ◽

Related Protein ◽

Human Term Placenta ◽

Parathyroid Hormone Related Protein ◽

Spontaneous Labour

Abstract Parathyroid hormone-related protein (PTHrP), the hypercalcaemia of malignacy factor, is expressed in the tissues of the human uteroplacental unit, including the placenta, amnion and chorion. We have used three region-specific immunoassays to quantitate and compare the distribution of PTHrP in tissues obtained at term following spontaneous labour and vaginal delivery or elective Caesarean section. In non-labouring women highest PTHrP(1–86) and (37–67) immunoreactivity was found in amnion covering the placenta, rather than the decidua parietalis of the uterus (reflected amnion) (median 1020 vs 451 fmol/g; 2181 vs 1444 fmol/g respectively). In labouring women, the PTHrP(1–86) concentration in reflected amnion was inversely correlated with the interval between rupture of the membranes and delivery. Tissue PTHrP(1–86) concentrations were lower in placenta than in chorion and amnion (medians 12, 109 and 664 fmol/g respectively) and, in all tissues, PTHrP(1–34) and (37–67) concentrations were significantly higher than that of PTHrP(1–86). Bioactive PTHrP(1–34) was detected in placenta, chorion and amnion using the ROS cell bioassay. The PTHrP(1–86) concentration (mean ± s.e.m.=41·4 ± 4·5 pmol/l) was high in amniotic fluid at term, although in maternal and cord plasma levels were only modestly increased. The molecular forms of PTHrP present in tissues and amniotic fluid were investigated by column chromatography which confirmed its molecular heterogeneity and suggested that processing is tissue-specific and occurs at both amino- and carboxy-terminals of the peptide. Journal of Endocrinology (1994) 142, 217–224

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Parathyroid hormone-related protein (PTHrP) mRNA splicing and parathyroid hormone/PTHrP receptor mRNA expression in human placenta and fetal membranes

Journal of Molecular Endocrinology ◽

10.1677/jme.0.0210225 ◽

1998 ◽

Vol 21 (2) ◽

pp. 225-234 ◽

Cited By ~ 14

Author(s):

NE Curtis ◽

RJ Thomas ◽

MT Gillespie ◽

RG King ◽

GE Rice ◽

...

Keyword(s):

Parathyroid Hormone ◽

Mrna Expression ◽

Late Pregnancy ◽

Mrna Splicing ◽

Fetal Membranes ◽

Related Protein ◽

Receptor Mrna ◽

Parathyroid Hormone Related Protein ◽

Pthrp Expression ◽

Pthrp Receptor

During human pregnancy, parathyroid hormone-related protein (PTHrP) and parathyroid hormone (PTH)/PTHrP receptor are produced by the uterus, placenta, fetal membranes (amnion and chorion) and developing fetus. PTHrP alternative 3' mRNA splicing results in transcripts which encode three PTHrP isoforms and have been identified in amnion. Uteroplacental PTHrP expression is greatest in amnion and increases dramatically during late pregnancy. The aims of this study were to determine PTH/PTHrP receptor mRNA expression at preterm and term gestations and to determine 3' alternative splicing patterns in placenta, amnion and choriodecidua at preterm and term gestations. Using semiquantitative reverse transcription-polymerase chain reaction, PTHrP and PTH/PTHrP receptor transcripts were identified in preterm (n=5) and term (n=7) gestational tissues. PTH/PTHrP receptor mRNA expression did not differ between tissue types or change with advancing gestation. In contrast, PTHrP expression in the same tissues increased with advancing gestation and was significantly greater in amnion than in placenta and choriodecidua. Thus PTHrP, although produced predominantly in amnion, may act in amnion and other tissues including placenta, choriodecidua and myometrium. In amnion over placenta, transcripts encoding PTHrP 1-139 and 1-173 were detected in some preterm and all term samples and those encoding PTHrP 1-141 were detected in all samples. Similar results were obtained for reflected amnion. In placenta and choriodecidua, PTHrP 1-139 and 1-173 transcripts were undetectable or of low abundance. PTHrP 1-141 transcripts were detected in some placenta and choriodecidua samples. In summary, transcripts encoding PTHrP 1-141 appeared to be more abundantly expressed than those encoding PTHrP 1-139 or 1-173. However, the up-regulation of PTHrP expression in amnion at term may involve each of the alternative 3' mRNA splicing pathways since transcripts for each isoform appeared to be more consistently expressed at term.

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