EFFECTS OF CELLULAR INTERACTIONS ON CALCIUM DYNAMICS IN PROLACTIN-SECRETING CELLS

Signals derived from other pituitary cells can have a dramatic effect on PRL gene expression and secretion by mammotropes. However, the intr acellular mechanisms by which these effects are manifested on the targ et cell remain unexplored. Inasmuch as calcium is a key modulator of b oth gene expression and hormone export in mammotropes, we evaluated th e effects of cell to cell contact vs. specific cellular interactions o n calcium dynamics within these cells. This was accomplished by digita l-imaging fluorescence microscopy of fura-2 in pituitary cells that we re isolated in culture (singles) or adjoining one other cell (doublets ). After calcium imaging, we then subjected cells to immunocytochemist ry for PRL. Doublets were further categorized into mammotropes attache d to another mammotrope (M-M) or to a nonmammotrope (M-nonM). We then calculated and compared Mean [Ca2+](i) values as well as Oscillation I ndices (which reflect the oscillatory behavior of cells) in singles an d doublets and found that they were not different (P > 0.05). However, the phenotype of the adjoining cell had a profound influence on both of these calcium parameters, such that the presence of one mammotrope could consistently decrease (P < 0.05) the Mean [Ca2+](i) value (39.17 +/- 3.83 vs. 56.24 +/- 5.56 in M-nonM) and Oscillation Index (10.19 /- 1.76 vs. 21.21 +/- 3.73 in M-nonM) of its neighboring counterpart. A more detailed analysis of oscillatory patterns in these cells reveal ed that nonoscillators were more abundant in M-M (23%) than in M-nonM (12%) doublets. Taken together, our results indicate that PRL-secretin g cells convey a signal that dampens the oscillatory behavior of neigh boring mammotropes. Thus, it appears that it is the phenotype rather t han the physical presence of a neighbor that controls intercellular re gulation of calcium dynamics among mammotropes.