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

Abstract

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 micrograms/l) increased PTHrP secretion after 24 h by 43%, 109% and 90%, respectively. Insulin-like growth factors I and II (100 micrograms/l), insulin (100 micrograms/l) and epidermal growth factor (EGF) (10 micrograms/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.

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

“…The findings of the present report are consistent with those of Papantoniou et al (1996), who reported low but detectable levels of PTHrP(1-86) that were not different from maternal values. Amniotic fluid PTHrP concentrations from term human pregnancy were found to be approximately 40 pmol/l, which is consistent with other reported values (Dvir et al 1995, Wlodek et al 1995. As there is no detectable PTHrP in fetal urine (Ferguson et al 1992, Wlodek et al 1995, it has been suggested that the PTHrP found in amniotic fluid is derived from the amnion.…”

Parathyroid hormone-related protein secretion is inhibited by oestradiol and stimulated by antioestrogens in KPL-3C human breast cancer cells

“…This hypothesis should be clarified both in vitro and in clinical studies. (Inoue et al, 1993;Endo et al, 1994;Dvir et al, 1995). In addition, a progestin, medroxyprogesterone acetate, dose-dependently inhibited PTHrP secretion from the PgR-positive KPL-3C cell line in our previous study (Kurebayashi et al, 1996).…”

“…Regulation of PTHrP secretion has been widely studied in cancer cell lines (Deftos et al, 1989;Emly et al, 1994;Endo et al, 1994;Merryman et al, 1994;Rizzoli et al, 1994), human T-cell lymphotrophic virus, type I-infected T cells (Inoue et al, 1993), normal and transformed keratinocytes Kremer et al, 1991;Allinson and Drucker, 1992), primary cultures of mammary epithelial cells (Thiede, 1989;Ferrari et al, 1992;Sebag et al, 1994), pituitary cells (Holt et al, 1994) and cultured amniotic fluid cells (Dvir et al, 1995). Steroid hormones, such as glucocorticoids, vitamin D and its analogues and progestins are reported to inhibit PTHrP secretion.…”

“…Two of these suggest that exogenous administration of 17f-oestradiol (E2) stimulated PTHrP expression in rat uterus in vivo (Thiede et al, 1991;Paspaliaris et al, 1992). One of these reports suggests that E2 induced a rapid and transient increase in PTHrP mRNA expression in rat pituitary cells (Holt et al, 1994); the other suggests that E2 has no effect on PTHrP secretion from cultured amniotic fluid cells (Dvir et al, 1995). To the best of our knowledge, no report has described the effects of oestrogen and antioestrogens on PTHrP secretion from oestrogen receptor (ER)-positive breast cancer cells.…”

Hypercalcemia in pregnancy – a multifaceted challenge: case reports and literature review

“…As the level of PTHrP was undetectable in the early postpartum, the placenta was probably the major source of secretion. However, considering the improvement of the woman' arthralgia only after the removal of the fibroma and knowing that secretion of PTHrP by the fibroma could be enhanced by estrogens and by human placental lactogen14, 15, 40, it is reasonable to think that the fibroma played an active part in the hypercalcemia. We therefore hope that following removal of the fibroma, the risk of recurrence of hypercalcemia in future pregnancies will be low.…”