CALCITONIN RECEPTOR IN HUMAN PLACENTAL SYNCYTIOTROPHOBLAST BRUSH-BORDER AND BASAL PLASMA-MEMBRANES

The physiology of calcium transport through the placenta has not been studied thoroughly. In particular, the effect of calcaemic hormones on this process has never been reported. In this paper we questioned if calcitonin, a hypocalcaemic hormone, is also implicated in the regulat ion of calcium transport by one of the placental syncytiotrophoblast b ipolar membranes. In order to investigate the implication of calcitoni n on calcium transport, we first studied whether this hormone binds to any of these bipolar membranes, i.e. purified syncytiotrophoblast bru sh border (facing the mother) and basal plasma membranes (facing the f etus). The initiation of binding of human [I-125]calcitonin to the two types of membranes was rapid and reached a steady state after 10 min of incubation at 37 degrees C. The number of binding sites and the aff inity of these receptors for the hormone were studied for each type of membrane, with concentrations of [I-125]calcitonin varying from 0.01 to 1.8 nM. Scatchard analysis revealed a single affinity binding site for human calcitonin with K(d)s of 0.83 +/- 0.09 nM and 0.67 +/- 0.26 nM for brush border and basal plasma membranes respectively. The maxim al number of receptors was significantly different (p < 0.001) in the two membranes: B-max of 66.64 +/- 9.15 fmol/mg protein for brush borde r membranes and 19.66 +/- 2.80 fmol/mg protein for basal plasma membra nes. Competitive displacement of [I-125]calcitonin with other ligands showed the following potencies between human calcitonin > salmon calci tonin > calcitonin gene-related peptides and segments analogues but no competition with some human calcitonin gene-related peptides fragment s. Half-maximal displacement concentration for human calcitonin was re ached at approximatively 1 nM for BBM and 0.1 nM for BPM. Calcitonin s timulated inositol phosphate production in both membranes by 175% and 330% in BBM and BPM, respectively. We conclude that calcitonin recepto rs are present in the two polar syncytiotrophoblast membranes, but are more abundant in brush border membranes, facing the mother. These res ults also suggest that in the placenta,both maternal and fetal calcito nin might intervene in ion transport and particularly calcium transpor t or on the intracellular metabolism of the placental syncytiotrophobl ast cells.