Effects of rosiglitazone--peroxisome proliferators-activated receptor gamma (PPARgamma) agonist on cell viability of human pituitary adenomas in vitro.
OBJECTIVE
Rosiglitazone (RGZ) belongs to thiazolidinediones - new class of antidiabetic drugs which are PPARgamma agonists. It was shown that tumoral tissue, including the pituitary adenomas, posses PPARgamma receptors. The activation of PPARgamma receptors inhibits tumour growth in rodents and induces the oncostatic effect on human cancer cell lines. The aim of the present study was to examine the anti-tumour effect of RGZ on human pituitary adenomas in vitro.


METHODS
Cells of eight pituitary adenomas removed neurosurgically were used to our experiment. Before the operation, the hormonal secretion of the tumour was estimated. After the surgery, the histological diagnosis and immunohistochemical detection of pituitary hormones and PPARgamma receptors were performed. The cells of pituitary tumours were exposed in the primary culture to RGZ at the concentrations of 10(-9)-10(-4) M for 24 hours. To measure the cell growth the modified colorimetric Mossman method detecting the cells viability was applied.


RESULTS
On the basis of the pre-operative diagnosis the 6 clinically non-functioning adenomas (CNFPA), one case of acromegaly and one case of Cushing's disease were recognized. In 5 out of 6 CNFPA the immunopositive reaction for different pituitary hormones such as: LH, HGH, PRL, FSH and alpha-subunit was detected. Expression of PPARgamma was found in all examined tumours. Rosiglitazone decreased the cell viability of all CNFPA and corticotropinoma for 20% or more. In somatotropinoma inhibition of the cell growth was about 13%. There is no correlation between PPARgamma expression and efficacy of rosiglitazone. THE MAIN FINDING: The obtained results indicate that RZG exerts a suppressive effect on the cell viability in non-functioning pituitary adenomas. The lack of correlation between PPARgamma expression and anti-tumoral effect of RZG suggests that the above-mentioned action of this compound is independent on PPARgamma expression.


CONCLUSIONS
Our data suggest that rosiglitazone may be useful in the treatment of non-functioning pituitary adenomas, but its efficacy in Cushing's disease and acromegaly requires further study.
Winczyk
Katarzyna
K
Department of Neuroendocrinology, Medical University of Łódź, Łódź, Poland. kwinczyk@os1.kappa.pl
Kunert-Radek
Jolanta
J
Gruszka
Anna
A
Radek
Maciej
M
Ławnicka
Hanna
H
Pawlikowski
Marek
M
D000172:Acromegaly / Q000209:etiology / Q000473:pathology; D000236:Adenoma / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D000368:Aged; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005260:Female; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000819:agonists*; D047748:Pituitary ACTH Hypersecretion / Q000209:etiology / Q000473:pathology; D010911:Pituitary Neoplasms / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone