Endocrine Abstracts

AMP-activated protein kinase (AMPK) activation decreased GH release and intracellular GH storage in rat pituitary cell cultures and reduced cell proliferation in rat pituitary adenomatous cells (GH3) cultures.

We investigated the effects of the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) as compared to somatostatin-14 on cell viability (MTT assay after 48-h) and GH secretion (over 24 h) in 16 human GH-secreting pituitary adenomas in vitro.

AICAR (0.4 mM) reduced cell viability in four adenomas out of fourteen (mean decrease vs control: 16±9%). Four adenomas were responsive to SS-14 (100 nM; mean decrease vs control: 15±6%). One adenoma was responsive to both somatostatin and AICAR. The effects of cotreatment with SS-14 and AICAR was investigated in eight adenomas. In two adenomas, the effects of AICAR+SS-14 did not exceed the effect of AICAR. In three adenomas which were not responsive to either AICAR or SS-14, the cotreatment was able to reduce cell viability by 27±5% vs control. Three adenomas were not responsive to any treatment. As to the effects on GH secretion, nine adenomas out of fourteen were responsive to AICAR (mean decrease 35±20%). Ten adenomas were responsive to SS-14 (mean decrease 40±15%). Seven adenomas were responsive to both AICAR and SS-14. Cotreatment exceeded the effect of single treatments in three adenomas out of seven.

Overnight treatment with AICAR induced a clear-cut increase in phospho-(threonine-172) AMPK (activated AMPK) whereas SS-14 did not alter significantly AMPK phosphorylation in cultured human adenomas.

In GH3 cells, AICAR reduced the activity of p70S6 kinase, which plays an important role in cell growth. SS-14 did not affect significantly AMPK phosphorylation and p70S6K activity but it was able to enhance the inhibitory effect of AICAR on p70S6K.

Our studies suggest that AMPK activators and SS-14 may cooperate in the control of a subset of GH-secreting pituitary adenomas in vitro.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.