Patey Prize 05

Background: Primary HPT predominately affects females and has a peak incidence at the perimenopausal period. This has led to speculations that an estrogen imbalance may have a role in this condition. We have previously demonstrated the importance of the insulin-like growth factor (IGF) axis in HPT. The SERM, tamoxifen (tam) has been shown to modulate the IGF axis. We propose to examine the interactions of SERMs and IGF in a primary parathyroid cell culture model. Methods: Estrogen (E2) receptors were evaluated by Western immuno-ligand blotting. Sixteen parathyroid glands from 14 patients were included. Following adhesion, the cells were transferred to serum free media and dosed once with IGF (I or II) ± estrogen ± SERMs (Tam), faslodex (fas, ICI 182780)) for 96 h. Proliferation was assessed by measuring tritiated thymidine incorporation. Results: Both primary (1) and secondary (2) HPT express α and β ERs. 1HPT and 2HPT had comparable responses and were analysed together. Compared with control (100%), IGFs (I & II) induced a significant increase in DNA synthesis. E2 at 10−8 and 10−7m (physiological range) inhibited DNA synthesis but had no significant effects on IGF (I & II) (P > 0.05). Tam inhibited basal DNA synthesis (P < 0.05) and abolished the effects of both IGF I and II (P < 0.05). To clarify whether these effects can be ascribed to Tam's ER antagonist property, Fas (a pure ER antagonist) was examined. Fas at 10−7m inhibited both IGF I and II (P < 0.05). Conclusions: Tam and Fas are capable of reducing basal and IGF stimulated DNA synthesis. There are obvious implications for cancer biology as well as therapeutic potential for SERMs in HPT.