The pathogenesis of gonadotrophin secreting pituitary tumours (gonadotrophinomas) remains poorly understood. Bone morphogenetic proteins (BMPs) are important for the control of cell proliferation and differentiation and BMP2 is essential for commitment of undifferentiated pituitary cells to the gonadotroph cell lineage. In addition, BMPs have been implicated in tumourigenesis in a variety of tissues, associated with up-regulated expression of Id (Inhibitors of differentiation) proteins and effects on cell proliferation. We have previously demonstrated BMP receptor expression in the well characterised LβT2 gonadotroph cell line and now report the effects of BMP2 on Id1 and Id3 expression in these cells. LβT2 cells were incubated in the absence or presence of BMP2 (10200 ng/ml) for 4 hours. Basal expression of both Id1 and Id3 mRNA was observed in these cells with a significant dose-dependent stimulation of Id1 and Id3 mRNA documented by quantitative real time PCR. PCR product identity was confirmed by direct sequencing. Maximal upregulation of Id1 (7.53 fold +/− 2.29 P<0.001) and Id3 (8.94 fold +/− 2.57 P<0.001) was seen with BMP2 at 100 ng/ml. Subsequent time course experiments showed that this stimulatory action of BMP2 was detectable after 2 hours for both Id1 (22.5 fold +/− 7.3 P<0.001) and Id3 (17.5 fold +/− 2.0 P<0.05). Our studies demonstrate that Id1 and Id3 are present in pituitary gonadotroph cells and that their expression levels are regulated by BMP2.
06 - 07 Nov 2006
Society for Endocrinology