The
thiazolidinedione derivative
CGP 19984 has previously been shown to suppress the growth of
hormone-dependent mammary and prostatic
tumors, primarily by reducing
gonadotropin and subsequently gonadal
steroid secretion. The present study examines the effects of
CGP 19984 on the growth and
hormone secretion of the autonomous, but
estrogen-responsive, MtT-W10 mammosomatotropic transplantable rat
pituitary tumor. Intact
tumor-bearing Wistar/Furth female rats were administered vehicle or 25, 100, or 250 mg/kg
CGP 19984 p.o., 5 x week for 4 weeks.
CGP 19984 was found to significantly reduce MtT-W10
tumor growth and weight and reduce
prolactin and
growth hormone (GH) secretion in a dose-responsive manner. A similar study in ovariectomized rats also showed that
CGP 19984 treatment suppressed MtT-W10
pituitary tumor growth, weight and
hormone secretion in a dose-responsive manner, suggesting a direct inhibitory action of this
drug on the
tumor. In a third study, bromocryptine (
CB-154; 5 mg/kg) and
CGP 19984 (50 mg/kg) were both found to be effective in suppressing growth of the MtT-W10
tumor in intact female rats. However, rats treated with
CGP 19984 alone had reduced serum and
tumor GH and
prolactin concentrations, while rats treated with
CB-154 alone had reduced serum and
tumor prolactin, but no change in GH concentrations. These results suggest that
CGP 19984 effectively inhibits growth and
hormone secretion of the autonomous MtT-W10
pituitary tumor by apparently suppressing both somatotropic and lactotropic cell populations within the
tumor. Furthermore, these findings indicate that
CGP 19984 may be an effective alternative to
CB-154 in the clinical treatment of
prolactin-producing
adenomas, as well as other types of
pituitary adenomas.