ANGIOTENSIN-II-INDUCED CA2-RELEASE IN NORMAL AND HYPERPLASTIC PITUITARY-CELLS( MOBILIZATION AND PROLACTIN)

We evaluated the effects of angiotensin II (ANG II) and its antagonist s on prolactin release! intracellular calcium ([Ca2+](i)) mobilization , and [H-3]thymidine uptake in cells from normal rat pituitaries and f rom estrogen-induced pituitary tumors. ANG II (10(-7) to 10(-9) M) inc reased prolactin release significantly in control and not in tumoral c ells. In control cells, ANG II (10(-6) to 10(-9) M) produced an immedi ate spike of [Ca2+](i) followed by a plateau. Spike levels rose signif icantly between 10(-10) and 10(-8) M ANG II, whereas the onset of the spike was retarded with decreasing concentrations. In tumoral cells, A NG II did not produce a spike phase even at 10(-6) M. ANG II-induced p rolactin release and calcium mobilization were blocked by losartan (AT (1) receptor antagonist) and not by PD-123319 (AT(1) antagonist). Fina lly, [H-3]thymidine uptake was not modified by ANG II (10(-7) to 10(-1 0) M) or its antagonists in either group. Our results suggest that chr onic in vivo estrogenic treatment alters in vitro pituitary response t o ANG II. Alterations might function to limit excessive prolactin secr etion of hypersecreting tumors. Besides, ANG II does not modify DNA sy nthesis in vitro of cells from normal or tumor-derived hypophyses.