angiotensin-i and Pituitary-Neoplasms

We investigated the effects of angiotensin peptides on the breakdown of specific membrane phospholipids, the inositol lipids, in anterior pituitary cells in culture, measuring the water-soluble products (inositol phosphates) produced during the cleavage of phosphoinositides by phospholipase C. Both angiotensin II and angiotensin I in the presence of 10 mM LiCl potently increased, in a concentration-dependent manner, total [3H]inositol phosphate and PRL release in cultured rat anterior pituitary cells. The release of LH, TSH, or GH was not significantly enhanced by the peptides. The effect on inositol phosphate accumulation was significant at 0.01 nM, and maximal stimulation (approximately 5-fold increase) occurred at 10 nM, with an ED50 of about 0.3 nM. The stimulatory effects of both angiotensin II and angiotensin I were antagonized by the receptor antagonists saralasin and Sar1,Ile8-angiotensin II. Moreover, 1 microM captopril, an inhibitor of angiotensin-converting enzyme, antagonized the effects of 0.1 and 1 nM angiotensin I, suggesting that the effect of angiotensin I on phosphoinositide breakdown and PRL release is dependent on prior conversion of angiotensin I to angiotensin II. The effect of angiotensin II was very rapid. Fractionation of the water-soluble inositol phosphates showed that angiotensin II significantly increased inositol bisphosphate and inositol triphosphate at 10 sec, whereas inositol monophosphate was increased only after 40 sec. These data indicate that in the pituitary, and presumably in the lactotroph, the binding of angiotensin II to specific membrane receptors provokes increased polyphosphoinositide hydrolysis, leading to increased production of intracellular messengers, i.e. inositol triphosphate and 1,2-diacylglycerol, responsible for the stimulation of PRL release.

Topics: 1-Sarcosine-8-Isoleucine Angiotensin II; Angiotensin I; Angiotensin II; Angiotensins; Animals; Captopril; Cells, Cultured; Female; Inositol Phosphates; Kinetics; Phosphatidylinositols; Pituitary Gland, Anterior; Pituitary Neoplasms; Prolactin; Rats; Rats, Inbred Strains; Receptors, Angiotensin; Saralasin

ACTH responsiveness in vitro to synthetic corticotropin-releasing factor (CRF), lysine-8-vasopressin, and cAMP was examined using superfusion of pituitary adenoma tissue and the nonadenomatous tissue from 16 patients with Cushing's disease. Sensitivity of adenomas to lysine-8-vasopressin and cAMP was similar to that of nonadenomatous tissues; however, sensitivity of adenomas to CRF was lower than that of nonadenomatous tissues in 7 of 16 patients. CRF-induced ACTH secretion from adenomas was inhibited by Ca2+-free medium in all instances and by dexamethasone and somatostatin in some. Angiotensins I and II stimulated ACTH secretion from both adenomas and nonadenomatous tissues, while angiotensin I-induced ACTH secretion was inhibited by angiotensin-converting enzyme inhibitor. These results suggest that the sensitivity of the pituitary corticotroph adenomas to CRF in some patients is low. This may be due to an abnormality of the step(s) before cAMP formation, such as the CRF receptor.

Topics: Adenoma; Adrenocorticotropic Hormone; Angiotensin I; Bromocriptine; Calcium; Corticotropin-Releasing Hormone; Cushing Syndrome; Cyclic AMP; Dexamethasone; Gonadotropin-Releasing Hormone; Humans; In Vitro Techniques; Lypressin; Pituitary Gland; Pituitary Neoplasms; Radioimmunoassay; Somatostatin; Thyrotropin-Releasing Hormone