Endocrine Abstracts

We have recently observed that the peroxisome proliferator receptor α was expressed by normal and tumoural pituitary tissues, in particular by somatotrophs. To elucidate its function, we have studied the effects of fenofibrate on cell proliferation and GH secretion in GH₃ cells.

Material and methods: GH₃ cells were grown in Ham’s F10 and treated for 24, 48 and 72 h by different concentrations of fenofibrate (12.5–50 μM). Cells were counted and GH concentration was measured in the medium by ELISA. GH concentration was then corrected by cell number. Real time RT-PCR and western blotting were performed on RNA and protein extracts to further analyse GH transcription and intracellular content. Cyclophilin B, which expression was not influenced by fenofibrate, was used as a housekeeping gene and a protein load control. Data were analysed by ANOVA with post-hoc Tukey analysis. P<0.05 was considered significant.

Results: A significant time- and dose-dependent decrease in cell proliferation was observed in treated cells, with a simultaneous increase in GH concentration. GH increase was maximal at 48 h and reached about three-folds at 25 μM and four-folds at 50 μM (P=0.004 and P=0.0004 vs controls, respectively). Analysis of GH mRNA at 48 h showed a bimodal response, with a significant increase in gene transcription at 25 μM (P=0.0094) and levels similar to control cells at 50 μM (P=0.002 vs 25 μM). Compared to control cells, a modest increase in intracellular GH content was also observed at 25 μM, with a modest decrease at 50 μM, respectively.

Conclusion: Fenofibrate in its therapeutic concentration range is able to reduce cell proliferation in GH₃ cells, with a dose-dependent increase in GH secretion which may reflect either an increased in GH synthesis (at low dose) or an increase in GH release (especially at high dose). It may be of interest to evaluate the clinical implications of these findings, especially in acromegalics.

Disclosure: This work was supported by The Italian Ministry for University and Research (MIUR) Grant 2009YJTBAZ_002.