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

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