A variety of endocrine and metabolic signals regulate pituitary cell function acting through the hypothalamus-pituitary neuroendocrine axes or directly at the pituitary level. The underlying intracellular transduction mechanisms in pituitary cells are still debated. AMP-activated protein kinase (AMPK) functions as a cellular sensor of low energy stores in all mammalian cells and promotes adaptive changes in response to calorie restriction. It is also regarded as a target for therapy of proliferative disorders. Various hormones and drugs can promote tissue-specific activation or inhibition of AMPK by enhancing or inhibiting AMPK phosphorylation, respectively. In the last ten years, evidence has accumulated that pituitary AMPK plays a role in the interplay between the activity of neuroendocrine axes and metabolic functions. AMPK was shown to be a potential point of integration of energy homeostasis with reproduction at the level of pituitary . Moreover, AMPK activation contributes to regulate the normal rat somatotroph cell function in-vitro. More recently, the hypoglycaemic agent metformin was shown to negatively modulate the basal hormone release from non-human primate somatotroph-, gonadotroph- and corticotroph cells in-vitro and to affect the expression of key receptors involved in the regulation of the distinct cell subtype function . Metformin targets different sites of cellular bioenergetics and is an indirect activator of AMPK. To this end, metformin enhances AMPK phosphorylation at threonine-172 in rat pituitary tumor cells. As to pituitary proliferative disorders, the direct AMPK activator AICAR reduces the growth of rat pituitary tumor cells. Actually, primary cell cultures from GH-secreting human pituitary adenomas were less sensitive to AICAR than rat cell lines. Our research group and other groups  have also investigated a possible role of metformin in the treatment of GH-secreting and prolactin-secreting tumors. Metformin can affect cell metabolism and cell signalling, and ultimately cell growth and function in-vitro when used at millimolar concentrations. Both AMPK-dependent and independent mechanisms are involved. The in-vitro effects of metformin may also help highlighting differences in metabolic requirements between pituitary adenomatous cells and normal cells.
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18 - 21 May 2019
European Society of Endocrinology