EFFECT OF A GONADOTROPIN-RELEASING-HORMONE ANALOG ON AN EXPERIMENTAL OVARIAN TUMOR - DIRECT AND INDIRECT ACTIONS

An ovary autotransplanted into the spleen of a bilaterally ovariectomi zed rat develops into a luteoma, which grows under constant gonadotrop in hyperstimulation. The effect of a long-acting GnRH agonist (GnRH-a) , on tumor growth and hormone secretion was investigated. Two experime ntal models were used: Model 1: GnRH-a (0.33 mg/rat sc) or estradiol v alerianate (50 mu g/rat sc injected once a week for four weeks) was ad ministered simultaneously with ovary implantation; Model 2: the drugs were administered after 1 month of tumor development. The treatment wi th estradiol was used as a control of tumor regression. Saline injecte d ovarian grafted rats and Sham operated animals were used as controls . In Model 1: The GnRH-a significantly inhibited tumor development (Po sitive tumors: Saline: 100% vs GnRH-a: 43%, p<0.01). In Model 2: the G nRH-a and estradiol significantly reduced the volume of one month old tumors (52% and 39% of initial volumes respectively, p<0.01). Gonadotr opin secretion was significantly inhibited or its increase blunted by the GnRH-a and by estradiol treatments in both models. Estradiol and p rogesterone in portal blood, which collects the steroids secreted by t he luteoma, were significantly reduced by GnRH-a treatment in both mod els. On the other hand, in tumor cells cultured ''in vitro'', the GnRH -a was able to inhibit the LH induced progesterone secretion in a conc entration dependent way. These results clearly show that the GnRH-a is effective in inhibiting tumor growth or reducing its volume, when alr eady developed; furthermore, it suppresses tumor steroid hormone produ ction. These actions were exerted at both the hypophyseal and tumor le vels.