Effect of a gonadotropin releasing hormone analog on an experimental ovarian tumor: direct and indirect actions.

Abstract

An ovary autotransplanted into the spleen of a bilaterally ovariectomized rat develops into a luteoma, which grows under constant gonadotropin hyperstimulation. The effect of a long-acting GnRH agonist (GnRH-a), on tumor growth and hormone secretion was investigated. Two experimental models were used: Model 1: GnRH-a (0.33 mg/rat sc) or estradiol valerianate (50 micrograms/rat sc injected once a week for four weeks) was administered simultaneously with ovary implantation; Model 2: the drugs were administered after 1 month of tumor development. The treatment with estradiol was used as a control of tumor regression. Saline injected ovarian grafted rats and Sham operated animals were used as controls. In Model 1: The GnRH-a significantly inhibited tumor development (Positive tumors: Saline: 100% vs GnRH-a: 43%, p < 0.01). In Model 2: the GnRH-a and estradiol significantly reduced the volume of one month old tumors (52% and 39% of initial volumes respectively, p < 0.01). Gonadotropin secretion was significantly inhibited or its increase blunted by the GnRH-a and by estradiol treatments in both models. Estradiol and progesterone in portal blood, which collects the steroids secreted by the luteoma, were significantly reduced by GnRH-a treatment in both models. On the other hand, in tumor cells cultured "in vitro", the GnRH-a was able to inhibit the LH induced progesterone secretion in a concentration dependent way. These results clearly show that the GnRH-a is effective in inhibiting tumor growth or reducing its volume, when already developed; furthermore, it suppresses tumor steroid hormone production. These actions were exerted at both the hypophyseal and tumor levels.

• Authors: V A Lux-Lantos, S M Thyssen, A Chamson, C Libertun
• Journal: Life sciences (Life Sci) Vol. 57 Issue 3 Pg. 291-300 ( 1995) ISSN: 0024-3205 [Print] Netherlands
• PMID: 7596232 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Gonadotropin-Releasing Hormone
• Progesterone
• Estradiol
• Luteinizing Hormone
• Follicle Stimulating Hormone

Topics

• Animals
• Estradiol (blood)
• Female
• Follicle Stimulating Hormone (blood)
• Gonadotropin-Releasing Hormone (analogs & derivatives, pharmacology)
• Luteinizing Hormone (blood)
• Luteoma (drug therapy, pathology)
• Ovarian Neoplasms (drug therapy, metabolism, pathology)
• Progesterone (metabolism)
• Rats
• Rats, Sprague-Dawley
• Tumor Cells, Cultured