hrvatski

Učinak endotelina-3 na funkcionalnu morfologiju adenoma hipofize in vitro

Tissues of 35 human pituitary adenomas were used in the study. Out of them there were 13 clinically functioning, i.e. hormone secreting, tumors and 22 clinically non-functioning tumors ( denoted FAH and NFAH respectively). Tumor tissue was cultured in vitro as tissue explant cultures, and as monolayer cell cultures ( obtained after dispersion of the tumor tissue ). Tissue explants were used for evaluation of the effects of human ET3 on hormone secreting activity and morphology the tumors, while cell cultures of the respective tumors were performed to analyse effects of ET3 on the tumor cell growth monitored according the 3H-TdR incorporation. The results obtained showed that almost all the tumors, irrespective of their morphological features, posses ACTH secreting capacity, which was modified in a particular pattern by ET3. Namely, in presence of ET3 the release of ACTH from the tumors synthesizing abundant amount of the hormone was suppressed, while opposite to that, ET3 stimulated ACTH secretion from the tumors that showed low ACTH secreting capacity. Thus, ET3 activity did not depend on the type of the adenoma, but on its hormonal activity in vitro. Irrespective of the type of the tumor, ET3 did not influence TSH release, which appeared to be secreted in vitro both by FAH and NFAH explants. On the other hand, type of adenoma determined release of FSH and LH mainly from NFAH and STH and PRL mainly from FAH cells. Tumor, or cell type-dependent activity of ET3 on the release of these hormones was mainly suppressive, while electron-microscopy showed that ET3 stimulated: 1) release of the hormones pre-synthesied in vivo, 2) stimu-late synthesis of hormones de novo and 3) suppress the release of newly synthesized hormones. Furthermore, cell type independent stimulation of 3H-TdR incorporation was observed in presence of ET3 for almost all the tumors. Growth stimulating activity of ET3 was not rela-ted to the IH presence of p53, which itself was found only occasionally in some tumors. On the contrary, ET3 was IH detected in about one half of the tumors, both FAH and NFAH. Since addition of ET3 to the culture medium further increased the incidence of ET3 IH positive tissues, it was concluded that the adenoma cells posses certain ET3 binding capacity, indicating possible presence of ET3 receptors on tumor cells. This finding might be of particular relevance since ET3 is not considered as abundant factors in normal, nontumorous human pituitary gland. Thus, it seems that ET3 might be one of the factors regulating both proliferative and hormone secreting features of the pituitary adenomas, while it has to be evaluated if ET3 acts mainly as cellular, tissue or humoral regulatory factor.

adenomi; hipofiza; imunohistokemija; funkcionalna morfologija; ET-3; elektronska mikroskopija; kultura tkiva; neuropatologija

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