The rat LTW(m) Leydig cell tumor: cancer anorexia due to estrogen

Anorexia occurs in male rats bearing transplantable LTW(m) Leydig cell tumors. Previous studies had shown that this tumor caused decreased food consumption and weight loss within 2 weeks of implantation. Additional studies reported here demonstrate that this tumor had little anorectic effect in female rats, and that male rats with LTW(m) tumors had elevated concentrations of circulating estradiol and low levels of testosterone. The tumor was also anorexigenic in castrated male rats. Exogenous estrogen given in the form of sc implanted pellets of estradiol reduced weight gain in male rats in proportion to the dose of estradiol. Weight gain was reduced when the plasma estradiol concentration was as low as 49 +/- 3 pg/ml; control estradiol levels were 25 +/- 4 pg/ml. Similar effects were observed in male Zucker fatty rats. It was further demonstrated that the tumor is anorexigenic in ventromedial hypothalamus-lesioned rats, an effect previously observed in ventromedial hypothalamus-lesioned rats given exogenous estradiol. Carcass analysis revealed that tumor-bearing rats used a metabolic fuel mixture containing a higher percentage of fat-derived substrates compared to nonimplanted controls, suggesting that altered fuel utilization may contribute to the decreased weight gain of tumor-bearing rats. We conclude that the circulating substance responsible for LTW(m) tumor-induced anorexia in male rats is likely to be an estrogenic steroid.