Objectives: 

In the pituitary gland somatotrophs are 60% of the whole secretory population in normal Adenopituitary, however represents only 10-15% of pituitary adenomas and 9% of pituitary carcinomas. It has been proposed that senescence is an essential pathway in the postnatal pituitary that explains the intrinsic benignity of adenomas. Somatotrophs are the only pituitary secretory cells expressing the dependence receptor RET, its co-receptor GFRa 1 and ligand GDNF, both in human and rats. RET, in absence of GDNF, becomes intracellulary processed inducing strong Pit-1 expression leading a direct regulation of the p19 Arf promoter and induces a p53 accumulation and apoptosis, in somatotroph cell line as well as in Adenopituitary primary culture, both from rat. For that reason would be important to determine whether the RET-induced apoptotic pathway is conserved in human samples, mainly in GH secreting adenomas.

Materials: 

Anterior pituitaries were dispersed into single cells by enzymatic and mechanical disruption from Human Pituitary tumor samples. Acromegaly and Non Functioning NFPA were used, obtaining cultures which were seeded in complete medium (DMEM/HAMF12/10%FBS),followed by 24h deprivation (0,5%FBS) ± GDNF 100ng/ml. We determined apoptosis percentage with Hoechst 33258 staining and protein expression by Western blot and Immunofluorescence.

Results: 

After 24h deprivation we observed an apoptotic peak just in Acromegaly culture, obtaining a 40% of apoptosis increase in deprivated samples from GH secreting adenomas although this effect was significant abolished after GDNF treatment, suggesting a RET-induced apoptosis and supported by RET and Pit-1 expression only in Acromegaly versus NFPA samples.

Conclusions: 

RET/Pit-1/apoptosis pathway would be the key link explaining the balance of somatotrophs during the whole postnatal life for its physiological function. This somatotroph-specific control would explain the low number of GH secreting adenomas in spite of being the most abundant type of cell.