ENDOTHELIN EXPRESSION IN NORMAL HUMAN ANTERIOR PITUITARIES AND PITUITARY-ADENOMAS

Endothelins (ETs) ale important regulators of growth and function in m any endocrine tissues. This study was designed to verify the expressio n of ETs in a series of normal human pituitaries and pituitary adenoma s. We examined 13 normal pituitaries and 58 pituitary adenomas for the presence of immunoreactive (ir) ET-1 and ET-3. No ir-ET-1 was detecte d in any of the 13 normal pituitaries, whereas ir-ET-3 was observed in 4 of 13 (31%) cases. In contrast, 48% (28 of 58) of pituitary adenoma s display immunoreactivity for ET-1, whereas 31% (18 of 58) show immun oreactivity for ET-3. With respect to the type of tumors, staining was as follows: nonfunctioning adenomas: ET-1, 14 of 33; ET-3, 9 of 33; s omatotropinomas: ET-1, 8 of 16; ET-3, 6 of 16; corticotropinomas: ET-1 , 5 of 5; ET-3, 2 of 5; and prolactinomas: ET-1, 1 of 4; ET-3, 1 of 4. Using double immunostaining, we found the colocalization of ET-3 in n ormal pituitaries and of ET-1 and ET-3 in pituitaries adenomas in each hormone-secreting cell. In Cushing adenomas, ET-1 was coexpressed in corticotropic cells in all 5 cases (100%). In the same tumors, by reve rse transcriptase polymerase chain reaction, we investigated the prese nce of ET-1 and ET-3 messenger ribonucleic acids and found that they a re expressed, respectively, in 18 of 21 and 7 of 11 tumors examined. O ur findings demonstrate that pituitary adenomas frequently display ET- 1 as well as ET-3 immunoreactivity, in contrast to normal pituitaries, in which only ET-3 was found. We showed the intratumoral presence of ET messenger ribonucleic acids, which indicates the production by tumo r itself, rather than passive uptake or binding of ET peptide synthesi zed elsewhere.