The effects of
gonadotropin-releasing hormone (
GnRH) and
GnRH-associated peptide (GAP) on cytosolic free
calcium concentration ([Ca(2+)](i)) were investigated in 20 human nonfunctioning
pituitary adenomas. We divided these
tumors into three classes according to their response pattern to hypothalamic
peptides. In type I
adenomas (8 out of 20
adenomas),
GnRH and GAP mobilized intracellular
calcium ions stored in a
thapsigargin (TG)-sensitive store. For the same concentration of agonist, two distinct patterns of
GnRH-GAP-induced Ca(2+) mobilization were observed (1) sinusoidal oscillations, and (2) monophasic transient. The latter is followed by a
protein kinase C (PKC)-dependent increase in
calcium influx through L-type channels. In type II
adenomas (7 out of 20
adenomas),
GnRH and GAP only stimulate
calcium influx through
dihydropyridine-sensitive Ca(2+) channels by a PKC-dependent mechanism. TG (1 μM) did not affect [Ca(2+)](i) in these cells, suggesting that they do not possess TG-sensitive Ca(2+) pools. All the effects of
GnRH and GAP were blocked by an inhibitor of
phospholipase C (PLC), suggesting that they were owing to the activation of the
phosphoinositide turnover. Type I and type II
adenoma cells showed spontaneous Ca(2+) oscillations that were blocked by
dihydropyridines and inhibition of PKC activity.
GnRH and GAP had no effect on the [Ca(2+)](i) of type III
adenoma cells that were also characterized by a low resting [Ca(2+)](i) and by the absence of spontaneous Ca(2+) fluctuations. K(+)-induced depolarization provoked a reduced Ca(2+) influx, whereas TG had no effect on the [Ca(2+)](i) of type III
adenoma cells. The variety of [Ca(2+)](i) response patterns makes these cells a good cell model for studying
calcium homeostasis in pituitary cells.