Endocrine Abstracts

Coordinated interaction between the neuroendocrine and immune systems is of paramount importance in regulating the host's response to inflammation and anoxic stress. Adenosine, released under such conditions in high concentration, modulates a number of inflammatory processes and can regulate the activity of the hypothalamo-pituitary-adrenal (HPA) axis. Although adenosine receptors (ARs) have been described in the pituitary gland, the distribution of the receptor subtypes (A1, A2A, A2B, A3) have not been defined. Accordingly, we have analysed the distribution of ARs in primary rat anterior pituitary (AP) cells, and pituitary endocrine and folliculostellate (FS) cell lines, and compared their effects on cell growth, VEGF and IL-6 expression. In AP and FS cells, adenosine and AR agonists (NECA, a universal AR agonist, and GCS 21680, a selective A2AR agonist) stimulated cAMP production with a potency order (NECA>adenosine>CGS 21680) indicating the presence of functional A2B receptors. This stimulation was not observed in endocrine cells where adenosine and the selective A1R agonist CCPA inhibited forskolin-stimulated cAMP production. mRNA and protein expression for the A2BR and A1R in FS cells, and the A1R in endocrine cells was confirmed by RT-PCR, immunocytochemistry and ligand binding. Adenosine stimulated the growth of FS cells via the A2BR but in higher concentration inhibited cell growth in endocrine cells by slowing progression through the cell cycle via the A1R. Adenosine and NECA stimulated IL-6 (up to 10- and 30-fold) and VEGF (up to 1.5- and 3-fold) production in FS but not in endocrine cells, effects that were reversible by dexamethasone. These data highlight the differential actions of adenosine in FS and endocrine cells mediated respectively via the A2B and A1 receptors. The effects on FS cell growth and IL-6 release support important paracrine and autocrine roles for adenosine in pituitary physiology and pathophysiology.