ECE2016 Eposter Presentations Pituitary - Basic (17 abstracts)
Temozolomide has no direct effect on the normal and pathological hormone production in the anterior pituitary and in pituitary tumors
Daniela Korthöwer 1 , Jose Monteserin-Garcia 1 , Yonghe Wu 2 , Johanna Stalla 1 , Michael Buchfelder 3 , Walter Rachinger 4 , Günter K. Stalla 1 & Ulrich Renner 1
1Max Planck Institute of Psychiatry, Clinical Neuroendocrinology, Munich, Germany; 2German Cancer Research Center, Molecular Genetics, Heidelberg, Germany; 3University of Erlangen-Nuremburg, Department of Neurosurgery, Erlangen, Germany; 4University of Munich, Department of Neurosurgery, Munich, Germany.
The chemotherapeutic agent temozolomide (TMZ) has been applied for the treatment of pituitary carcinomas, atypical pituitary adenomas and prolactinomas resistant to dopamine agonist treatment with considerable success. Both shrinkage of the tumors and a drop of excessive hormone production were observed in TMZ-responsive patients. In order to clarify whether the TMZ-induced suppression of hormone secretion was a consequence of tumor shrinkage or caused by direct effects on hormone production we comparatively studied the effect of TMZ on growth and hormone production in the ACTH-releasing AtT20 and in the GH/PRL-secreting GH3 cell lines, in a series of primary cell cultures of human endocrine-active pituitary adenomas and in cell cultures of normal rat pituitaries. In the rapidly growing AtT20 and GH3 cell lines TMZ treatment reduced both cell numbers and hormone secretion but had no effect on hormone production per cell demonstrating that the reduction of hormone secretion was a consequence of the inhibition of growth of these cells. In 11 hormone-secreting pituitary adenomas (5 somatotroph, 1 lactosomatotroph, 2 lactotroph, 2 corticotroph and 1 thyrotroph tumor), in which no or very little effects of TMZ on growth were observed, TMZ did not alter GH, PRL, ACTH and TSH secretion, respectively. Neither basal nor releasing-hormone stimulated secretion of ACTH and GH as well as basal or bromocriptine-suppressed PRL secretion was affected in rat pituitary cell cultures by TMZ. In conclusion, TMZ had no direct effect on hormone secretion in normal pituitary and pituitary tumors indicating that TMZ-induced suppression of hormone levels in patients with pituitary carcinomas may have been a consequence of tumor shrinkage.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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