AMP-activated protein kinase regulates normal rat somatotroph cell function and growth of rat pituitary adenomatous cell

AMP-activated protein kinase (AMPK) is
activated under conditions that deplete cellular ATP and
elevate AMP levels such as glucose deprivation and
hypoxia. The AMPK system is primarily thought of as a
regulator of metabolism and cell proliferation. Little is
known about the regulation and the effects of AMPK in
somatotroph cells. We present results from ‘‘in vitro’’
studies showing that AMPK activity has a role in regulating
somatotroph function in normal rat pituitary and is a
promising target for the development of new pharmacological
treatments affecting cell proliferation and viability
of pituitary adenomatous cells. In parallel, we show ‘‘in
vivo’’ data obtained in the rat suggesting that AMPK is an
intracellular transducer that may play a role in mediating
the effects of the pharmacological treatment with dexamethasone
on somatotrophs. In rat pituitary cell cultures,
the AMP analog AICAR induced a rapid and clear-cut
activation of AMPK. AICAR decreased GH release and
total cellular GH content. An appropriate level of AMPK
activation was essential for GH3 adenomatous cells.
Remarkably, over-activation by AICAR induced apoptosis
of GH3 whereas the AMPK inhibitor compound C was
more effective at reducing cell proliferation. The role of
endocrine or paracrine factors in regulating AMPK phosphorylation
and activity in GH3 cells has been also studied.
As to ‘‘in vivo’’ studies, western blot analysis revealed
a significant decrease of phosphorylated AMPK alphasubunit
in pituitary homogenates of DEX-treated rats
versus controls, suggesting reduced AMPK activity. In
conclusion, our studies showed that AMPK has a role in
regulating somatotroph function in normal rat pituitary and
proliferation of pituitary adenomatous cells.