EB-1089, A CALCITRIOL ANALOG, DECREASES FETAL CALCIUM CONTENT WHEN INJECTED INTO PREGNANT RATS

EB 1089 is a calcitriol analogue with low calcaemic activity, which in hibits parathyroid hormone-related peptide (PTHrP) secretion in rats i mplanted with the Leydig cell tumour H-500. We have studied its effect on maternal and fetal plasma PTHrP concentrations and on fetal calciu m and phosphorus contents in rats. Three groups of six pregnant rats w ere injected I.P. daily with EB 1089 (0.10, 0.25 and 0.50 mu g kg(-1) in groups 1, 2 and 3, respectively, from day 12 to day 20 of gestation ). The control group received an equal volume of solvent alone. On day 21 of gestation the animals were anaesthetized with chloral hydrate a nd blood samples were taken. Fetuses were collected, weighed and ashed for Ca and P measurements. PTHrP concentrations were measured by radi oimmunoassay (RIA) in maternal and fetal plasma. Calcium content (mg ( g fetal wt)(-1); mean +/- S.E.M.) in control fetuses was not different from that measured in fetuses from dams given the lowest dose of EB 1 089, but was higher than that in fetuses from rats injected with EB 10 89 at 0.25 mu g kg(-1) (1.18 +/- 0.20; P < 0.05) or 0.50 mu g kg(-1) ( 1.08 +/- 0.29; P < 0.05). There was no difference in fetal P content b etween any of the groups of rats. The PTHrP concentration (pg equivale nts human PTHrP(1-34) fragment ml(-1)) in maternal plasma from control rats (1.70 +/- 0.50) was not different from that in maternal plasma o f rats given the lowest dose of EB 1089 (1.44 +/- 0.63). In these two groups fetal plasma PTHrP concentration (6.93 +/- 1.71 and 4.59 +/- 1. 30, respectively) was significantly higher than that measured in the d ams. PTHrP was undetectable in both fetal and maternal plasma from the other two groups, i.e. those in which fetal Ca content was reduced. T hus inhibition of PTHrP secretion by EB 1089 might be responsible for a decrease in fetal Ca content.