Endocrine Abstracts

The pathogenesis of gonadotrophin secreting pituitary tumours (gonadotrophinomas) remains poorly understood. BMP2, known to be important in the control of cell proliferation and differentiation, is essential for commitment of undifferentiated pituitary cells to the gonadotroph cell lineage. Attenuation of its expression is critical in allowing terminal differentiation. BMPs are associated with up-regulated expression of Id (Inhibitors of differentiation) proteins with predicted stimulatory effects on cell proliferation and have been implicated in tumourigenesis in a variety of tissues. We have previously demonstrated BMP receptor expression in the well characterised LβT2 gonadotroph cell line and have reported BMP2 dependent upregulation of Id1 and Id3 mRNA in this cell line. We now show the effects of Noggin, a specific inhibitor of BMP2 receptor interaction, on BMP2 induced expression of Id1 and Id3 and on cell proliferation. LβT2 cells were incubated in the presence or absence of Noggin (100, 1000 ng/ml), with BMP2 (100 ng/ml) for 4 h. Using western blot, we show a BMP2 dependent increase in Id1 protein expression that is reduced following pretreatment with Noggin at 1000 ng/ml (0.62 fold decrease ±0.072 P<0.05). Equivalent changes are not seen in the expression of Id3 protein. Following incubation of LβT2 cells for 48 h with BMP2 in the presence or absence of Noggin (100, 1000 ng/ml), we have demonstrated an increase in LβT2 cell proliferation with BMP2 using radiolabelled thymidine incorporation. This effect was attenuated by pretreatment with Noggin, although this did not achieve significance. Our studies demonstrate that BMP2 increases Id1 protein expression and cell proliferation in LβT2 cells and that this effect is BMP2 receptor dependent.