Angiotensin II-induced Ca21 mobilization and prolactin release in normal and hyperplastic pituitary cells

Dı́az-Torga, Graciela, Arturo González Iglesias, Rita Achával-Zaia, Carlos Libertun, and Damasia BecúVillalobos. Angiotensin II-induced Ca21 mobilization and prolactin release in normal and hyperplastic pituitary cells. Am. J. Physiol. 274 (Endocrinol. Metab. 37): E534–E540, 1998.—We evaluated the effects of angiotensin II (ANG II) and its antagonists on prolactin release, intracellular calcium ([Ca]i) mobilization, and [3H]thymidine uptake in cells from normal rat pituitaries and from estrogen-induced pituitary tumors. ANG II (1027 to 1029 M) increased prolactin release significantly in control and not in tumoral cells. In control cells, ANG II (1026 to 1029 M) produced an immediate spike of [Ca]i followed by a plateau. Spike levels rose significantly between 10210 and 1028 M ANG II, whereas the onset of the spike was retarded with decreasing concentrations. In tumoral cells, ANG II did not produce a spike phase even at 1026 M. ANG II-induced prolactin release and calcium mobilization were blocked by losartan (AT1 receptor antagonist) and not by PD-123319 (AT2 antagonist). Finally, [3H]thymidine uptake was not modified by ANG II (1027 to 10210 M) or its antagonists in either group. Our results suggest that chronic in vivo estrogenic treatment alters in vitro pituitary response to ANG II. Alterations might function to limit excessive prolactin secretion of hypersecreting tumors. Besides, ANG II does not modify DNA synthesis in vitro of cells from normal or tumor-derived hypophyses.