Effects of the Thiazolidinedione Derivative Cgp 19984 on Growth Mammosomatotropic Pituitary Tumor in Female Rats

نویسندگان

  • Alan R. Liss
  • Paul W. SYLVESTER
  • Paul J. UTZ
چکیده

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-W 10 mammosomatotropic transplantable rat pituitary tumor. Intact tumor-bearing WistarlFurth female rats were administered vehicle or 25, 100, or 250 mgl kg CGP 19984 p.0.. 5 x week for 4 weeks. CGP 19984 was found to significantly reduce MtT-W 10 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-W 10 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 mglkg) and CGP 19984 (50 mg/kg) were both found to be effective in suppressing growth of the MtT-W 10 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 CB154 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-W 10 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.

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تاریخ انتشار 2006