Parathyroid hormone-related protein in human term placenta and membranes

1994 ◽  
Vol 142 (2) ◽  
pp. 217-224 ◽  
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

scholarly journals Cloning of bovine parathyroid hormone-related protein (PTHrP) cDNA and expression of PTHrP mRNA in the bovine mammary gland

1998 ◽  
Vol 20 (2) ◽  
pp. 271-280 ◽  
Author(s):  
SF Wojcik ◽  
FL Schanbacher ◽  
LK McCauley ◽  
H Zhou ◽  
V Kartsogiannis ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Parathyroid Hormone ◽  
Cdna Library ◽  
Bovine Milk ◽  
Bovine Brain ◽  
Molecular Heterogeneity ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Lactating Mammary Gland ◽  
Brain Cdna Library

Parathyroid hormone-related protein (PTHrP) produced by the mammary gland has been postulated to have multiple functions in both the mother and neonate. In humans, alternative 3'-mRNA splicing and endoproteolytic processing result in multiple bioactive PTHrP peptides. Multiple PTHrP peptides also have been reported in bovine milk. To investigate the source of molecular heterogeneity of PTHrP in bovine milk, bovine PTHrP was cloned from a bovine brain cDNA library, sequenced and used to characterize the mammary PTHrP transcript. A 1065 bp clone (bP1) for bovine PTHrP was isolated from a brain cDNA library. The bP1 clone contained the entire coding sequence of PTHrP and 61 and 473 nucleotides of the 5'- and 3'-untranslated regions (UTRs) respectively. The predicted amino acid sequence of bovine PTHrP was 72-92% homologous to the sequences of chicken, rat, mouse, human, and canine PTHrP with the highest sequence divergence present in the C-terminal region of the peptide. The 5'- and 3'-UTRs of bovine brain PTHrP have a high degree of homology to exons 4 and 9 of human PTHrP respectively. PTHrP was expressed as a single 1200 nucleotide mRNA transcript in lactating bovine mammary tissue. RT-PCR using region-specific oligonucleotide primers derived from bP1 demonstrated that PTHrP mRNA transcripts in bovine brain and lactating mammary gland utilize the same 5'- and 3'-UTRs. Expression of PTHrP mRNA was localized to secretory and ductular epithelial cells within the lactating mammary gland, as detected using in situ hybridization. Expression of PTHrP mRNA was demonstrated in the mammary gland during late pregnancy and throughout lactation in cows.

Parathyroid hormone-related protein (PTHrP) concentrations in human amniotic fluid during gestation and at the time of labour

1995 ◽  
Vol 7 (6) ◽  
pp. 1509 ◽  
Author(s):  
ME Wlodek ◽  
PW Ho ◽  
GE Rice ◽  
JM Moseley ◽  
TJ Martin ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Amniotic Fluid ◽  
Gestational Age ◽  
Late Gestation ◽  
Physiological Significance ◽  
Fetal Membrane ◽  
Related Protein ◽  
Human Amniotic Fluid ◽  
Membrane Function ◽  
Parathyroid Hormone Related Protein

To establish the changes associated with gestational age and labour status in parathyroid hormone-related protein (PTHrP) concentrations in the amniotic fluid, human amniotic fluid was collected from non-labouring and labouring women at < 37 weeks of gestation (preterm) and at term (> or = 37 weeks). PTHrP was assayed by a specific N-terminal radioimmunoassay. PTHrP concentrations in amniotic fluid obtained from non-labouring women were significantly lower at preterm (15-36 weeks; 14.1 +/- 2.5 pmol L(-1); n = 11) than at term (37-42 weeks; 39.3 +/- 7.6 pmol L(-1); n = 16; P < 0.0009). Concentrations of PTHrP in amniotic fluid obtained from labouring women were also significantly lower at preterm (27-36 week; 12.2 +/- 4.7 pmol L(-1); n = 4; P < 0.01) than at term (37-42 weeks; 63. 8 +/- 19.6 pmol L(-1); n = 9). There were no significant changes in concentration associated with labour status, either at preterm or at term. The physiological significance of elevated amniotic fluid concentrations of PTHrP has yet to be established, but the data are consistent with the suggestion that PTHrP plays a role in fetal membrane function during late gestation.

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

1997 ◽  
Vol 154 (1) ◽  
pp. 103-112 ◽  
Author(s):  
N E Curtis ◽  
P W M Ho ◽  
R G King ◽  
W Farrugia ◽  
E K Moses ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Caesarean Section ◽  
Normal Vaginal Delivery ◽  
Smooth Muscle Relaxation ◽  
Fetal Membranes ◽  
Related Protein ◽  
Immunoreactive Protein ◽  
Parathyroid Hormone Related Protein ◽  
Gestational Tissues ◽  
Term Labour

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

Amniotic fluid and plasma levels of parathyroid hormone-related protein and hormonal modulation of its secretion by amniotic fluid cells

1995 ◽  
Vol 133 (3) ◽  
pp. 277-282 ◽  
Author(s):  
Rina Dvir ◽  
Avraham Golander ◽  
Niva Jaccard ◽  
Gideon Yedwab ◽  
Itzhak Otremski ◽  
...  
Keyword(s):  
Growth Factors ◽  
Parathyroid Hormone ◽  
Amniotic Fluid ◽  
Related Protein ◽  
Humoral Hypercalcemia Of Malignancy ◽  
Tel Aviv ◽  
Humoral Hypercalcemia ◽  
Parathyroid Hormone Related Protein ◽  
Amniotic Fluid Cells ◽  
Hormonal Modulation

Dvir R, Golander A, Jaccard N, Yedwab G, Otremski I, Spirer Z, Weisman Y. Amniotic fluid and plasma levels of parathyroid hormone-related protein and hormonal modulation of its secretion by amniotic fluid cells. Eur J Endocrinol 1995;133:277–82. ISSN 0804–4643 Parathyroid hormone-related (PTHrP), the major mediator of humoral hypercalcemia of malignancy, may also regulate placental calcium flux, uterine contraction and fetal tissue development. In the present study, we demonstrated that the mean immunoreactive PTHrP concentrations in amniotic fluid at mid-gestation (21.2 ± 3.7 pmol/l) and at term (19.0 ± 2.7 pmol/l) were 13-16-fold higher than levels measured in either fetal (1.6 ± 0.1 pmol/l) or maternal plasma (1.4 ± 0.3 pmol/l) at term and equal to levels found in plasma of patients with humoral hypercalcemia of malignancy. In vitro studies pointed to three possible sources of PTHrP in amniotic fluid: cultured amniotic fluid cells, cells derived from the amniotic membrane overlying the placenta and placental villous core mesenchymal cells. Treatment of cultured amniotic fluid cells with human prolactin, human placental lactogen (hPL) or human growth hormone (100 μg/l) increased PTHrP secretion after 24 h by 43%, 109% and 90%, respectively. Insulin-like growth factors I and II(100 μg/l), insulin (100 μg/l) and epidermal growth factor (EGF) (10 μg/l) increased PTHrP secretion by 53%, 46%, 68% and 118%, respectively. The stimulation of PTHrP secretion by EGF or by hPL was both time- and dose-dependent. In contrast, calcitriol and dexamethasone (10 nmol/l) decreased PTHrP secretion by 32% and 75%, respectively. Estradiol, progesterone, dihydrotestosterone and human chorionic gonadotropin had no effect on PTHrP secretion. These findings support the notion that PTHrP may play a physiological role in the uteroplacental unit and demonstrate that human amniotic fluid cells could be a useful model for studying the regulation of PTHrP production and secretion by hormones and growth factors. Y Weisman, Bone Disease Unit, Tel Aviv Medical Center, 6 Weizman Street, Tel Aviv 64239, Israel

Identification and partial characterization of parathyroid hormone-related protein in human and bovine milk

1990 ◽  
Vol 127 (1) ◽  
pp. 167-176 ◽  
Author(s):  
W. A. Ratcliffe ◽  
E. Green ◽  
J. Emly ◽  
S. Norbury ◽  
M. Lindsay ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Cyclic Amp ◽  
Molecular Species ◽  
Bovine Milk ◽  
Gel Filtration ◽  
Molecular Forms ◽  
Gel Chromatography ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein

ABSTRACT Parathyroid hormone-related protein (PTHrP) was measured in human and bovine milk by radioimmunoassay (RIA) and bioassay, and the molecular forms characterized by gel chromatography and immunoblotting of affinity-purified PTHrP. Mean immunoreactive PTHrP(1–34) concentrations were 23 and 87 μg/l in human and bovine milk respectively. Bioactive (BIO) PTHrP concentrations determined by cyclic AMP production by ROS 17/2·8 cells correlated significantly (P< 0·001) with those obtained by RIA (BIO = 1·04RIA−3·4, r = 0·939). Gel filtration of human and bovine milk identified several peaks with immunoactivity and bioactivity. Immunoblotting of affinity-purified PTHrP revealed multiple molecular species including components with mobilities similar to those of PTHrP and its subfragments. These studies confirm the presence of immuno- and bioactive PTHrP in milk and suggest that post-translational processing is complex and variable. Journal of Endocrinology (1990) 127, 167–176

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

2000 ◽  
Vol 165 (3) ◽  
pp. 657-662 ◽  
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.

Characterization of Parathyroid Hormone-Related Protein in the Human Term Placenta.

1992 ◽  
Vol 39 (6) ◽  
pp. 555-561 ◽  
Author(s):  
EMI ISHIKAWA ◽  
HIDEKI KATAKAMI ◽  
HIROYUKI HIDAKA ◽  
YOSHIHIKO USHIRODA ◽  
TOMOAKI IKEDA ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Related Protein ◽  
Human Term Placenta ◽  
Term Placenta ◽  
Parathyroid Hormone Related Protein
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