Angiotensin II-induced Ca2+ mobilization and prolactin release in normal and hyperplastic pituitary cells.
We evaluated the effects of angiotensin II (ANG II) and its antagonists on prolactin release, intracellular calcium ([Ca2+]i) mobilization, and [3H]thymidine uptake in cells from normal rat pituitaries and from estrogen-induced pituitary tumors. ANG II (10(-7) to 10(-9) M) increased prolactin release significantly in control and not in tumoral cells. In control cells, ANG II (10(-6) to 10(-9) M) produced an immediate spike of [Ca2+]i followed by a plateau. Spike levels rose significantly between 10(-10) and 10(-8) 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 10(-6) 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 (10(-7) to 10(-10) 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.
Díaz-Torga
G
G
Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas V, Buenos Aires, Argentina.
González Iglesias
A
A
Achával-Zaia
R
R
Libertun
C
C
Becú-Villalobos
D
D
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004261:DNA Replication; D004967:Estrogens; D005260:Female; D006965:Hyperplasia / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D015175:Prolactinoma / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000493:pharmacokinetics
D004967:Estrogens; D000804:Angiotensin II; D011388:Prolactin; D002118:Calcium; D013936:Thymidine