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 ◽  
...  

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.

1994 ◽  
Vol 142 (2) ◽  
pp. 217-224 ◽  
Author(s):  
S J Bowden ◽  
J F Emly ◽  
S V Hughes ◽  
G Powell ◽  
A Ahmed ◽  
...  

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


1995 ◽  
Vol 133 (3) ◽  
pp. 277-282 ◽  
Author(s):  
Rina Dvir ◽  
Avraham Golander ◽  
Niva Jaccard ◽  
Gideon Yedwab ◽  
Itzhak Otremski ◽  
...  

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


2000 ◽  
Vol 165 (3) ◽  
pp. 657-662 ◽  
Author(s):  
W Farrugia ◽  
PW Ho ◽  
GE Rice ◽  
JM Moseley ◽  
M Permezel ◽  
...  

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.


1996 ◽  
Vol 8 (2) ◽  
pp. 231 ◽  
Author(s):  
MD Mitchell ◽  
C Hunter ◽  
DJ Dudley ◽  
MW Varner

It has been determined whether amniotic fluid concentrations of parathyroid hormone-related protein (PTHrP) change with labour. An evaluation of which cells from intrauterine tissues might produce PTHrP has also been conducted. Amniotic fluid was obtained by amniocentesis from women: (1) at term, not in labour; (2) in normal term labour; (3) in preterm labour, undelivered within one week; (4) in preterm labour, delivered within one week; (5) in preterm labour associated with clinical chorioamnionitis; and (6) who were gestation-matched controls for chorioamnionitis patients-women in this group were similar to those in Group 4 but were different patients. Amnion, chorion, and decidual cells were grown by standard techniques and incubated with interleukin-1 beta (IL-1 beta). PTHrP was assayed in duplicate samples of amniotic fluid or tissue culture media using an immunoradiometric assay. There was a significant reduction in amniotic fluid concentrations of PTHrP during labour at term. Preterm labour was not associated with significant changes in amniotic fluid concentrations of PTHrP although a trend for reduced concentrations was observed. Amnion and chorion produced measurable quantities of PTHrP and rates of production were increased by treatment with IL-1 beta. Decidual cells did not produce detectable amounts of PTHrP. Hence, labour at term is associated with a decrease in amniotic fluid PTHrP concentrations that may reflect reduced amnion production, which in turn may play a permissive or active role in the mechanism(s) of parturition. These data support the view that the mechanisms that control term and preterm labour may be regulated differently.


1998 ◽  
Vol 5 (3) ◽  
pp. 127-131
Author(s):  
Wen X. Wu ◽  
Mary E. Bruns ◽  
D. Bruns ◽  
Regina Seaner ◽  
Peter W. Nathanielsz ◽  
...  

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