PARATHYROID HORMONE-RELATED PROTEIN (PTHRP) MESSENGER-RNA SPLICING AND PARATHYROID HORMONE PTHRP RECEPTOR MESSENGER-RNA EXPRESSION IN HUMANPLACENTA AND FETAL MEMBRANES

During human pregnancy, parathyroid hormone-related protein (PTHrP) an d parathyroid hormone (PTH)/PTHrP receptor are produced by the uterus, placenta, fetal membranes (amnion and chorion) and developing fetus. PTHrP alternative 3' mRNA splicing results in transcripts which encode three PTHrP isoforms and have been identified in amnion. Uteroplacent al PTHrP expression is greatest in amnion and increases dramatically d uring late pregnancy. The aims of this study were to determine PTH/PTH rP receptor mRNA expression at preterm and term gestations and to dete rmine 3' alternative splicing patterns in placenta, amnion and choriod ecidua at preterm and term gestations. Using semiquantitative reverse transcription-polymerase chain reaction, PTHrP and PTH/PTHrP receptor transcripts were identified in preterm (n=5) and term (n=7) gestationa l tissues. PTH/PTHrP receptor mRNA expression did not differ between t issue types or change with advancing gestation. In contrast, PTHrP exp ression in the same tissues increased with advancing gestation and was significantly greater in amnion than in placenta and choriodecidua. T hus PTHrP, although produced predominantly in amnion, may act in amnio n and other tissues including placenta, choriodecidua, and myometrium. In amnion over placenta, transcripts encoding PTHrP 1-139 and 1-173 w ere detected in some preterm and all term samples and those encoding P THrP 1-141 were detected in all samples. Similar results were obtained for reflected amnon. In placenta and choriodecidua, PTHrP 1-139 and 1 -173 transcripts were undetectable or of low abundance. PTHrP 1-141 tr anscripts were detected in some placenta and choriodecidua samples. In summary, transcripts encoding PTHrP 1-141 appeared to be more abundan tly expressed than those encoding PTHrP 1-139 or 1-173. However, the u p-regulation of PTHrP expression in amnion at term may involve each of the alternative 3' mRNA splicing pathways since transcripts for each isoform appeared to be more consistently expressed at term.