Hypothalamic peptides modulate cytosolic free Ca2+ levels and adenylyl cyclase activity in human nonfunctioning pituitary adenomas

The effects of hypothalamic peptides (TRH, GnRH, arginine vasopressin, vasoactive intestinal peptide, GHRH, CRH, and SRIH) on cytosolic free calcium concentrations ([Ca²⁺]i) and adenylyl cyclase (AC) activity were evaluated in 12 nonfunctioning pituitary adenomas. TRH, GnRH, and arginine vasopressin induced a marked [Ca²⁺]i rise in 10/12, 4/ 12, and 2/5 tumors, respectively. The transients induced by these peptides were due to both Ca²⁺ mobilization from the intracellular stores and Ca²⁺ influx from the extracellular medium. AC activity was evaluated in 10 adenomas; 1 μM vasoactive intestinal peptide induced a 2- to 6-fold stimulation of the enzyme activity in all tumors, while neither GHRH nor CRH were effective. Moreover, in 5/10 tumors 1 μM SRIH reduced both AC activity and [Ca²⁺]i, while in 2/10 the peptide caused a significant rise in [Ca²⁺]i despite the AC inhibition and in 3/10 SRIH did not modify either AC activity or [Ca²⁺]i. This study indicates that in nonfunctioning pituitary adenomas a wide spectrum of hypothalamic peptides modulate [Ca²⁺]i and AC activity. Moreover, the presence of biologically active receptors may offer a possible target for therapeutic intervention.