ANALYSIS OF THE IN-VITRO SECRETORY ACTIVITY OF HUMAN PITUITARY-ADENOMAS - MODIFICATION OF CORTICOTROPIN RELEASE FROM ADENOMA TISSUE EXPLANTCULTURES BY ADDITION OF A HUMAN PLASMA ULTRAFILTRATE BIOACTIVE FRACTION

The lack of control of tumour behaviour is manifested in different way s, depending primarily on the type of tumour. This results in numerous problems of tumour diagnosis and therapy. In the case of ''benign'' t umours, like pituitary adenomas, in vitro studies are often used for e valuation of the tumour. The use of tissue explant cultures of human p ituitary adenomas and the comparison of the feature of cultured tumour s with their behaviour in vivo showed that corticotropin is released n ot only from the tumours associated with Cushing's disease, but also f rom clinically non-functioning tumours. Hence, it was supposed that th e release of corticotropin in vivo from non-secreting tumours is proba bly under the influence of certain neuroendocrine and/or systemic humo ral factors. To test this possibility, samples of 22 tumours were cult ured in plain culture medium or in the presence of the ''human plasma ultrafiltrate bioactive fraction'' (tentatively termed as TBP) prepare d by anion-exchange chromatography. In the presence of TBP the release of corticotropin was strongly inhibited in adenomas showing relativel y high spontaneous secreting activity in vitro (> 200 ng/l in 24 hours ), while immunohistochemistry of these tumours indicated accumulation of corticotropin inside the cells. In contrast, TBP stimulated cortico tropin release from tumours that showed relatively low basic corticotr opin release (< 200 ng/l in 24 hours), with no obvious change in cellu lar corticotropin immunoreactivity. Such a dual activity of TBP was no t observed for 8 samples of adenomas cultured in the presence of surro unding pituitary tissue, probably because TBP did not affect corticotr opin secretion by the normal pituitary cells (as indicated by immunohi stochemistry). From these results, it appears that TBP could be one of the humoral factors involved in the regulation of corticotropin relea se from pituitary adenoma tissue. Its possible involvement in the regu lation of corticotropin release from normal pituitary tissue, however, is uncertain.