Effects of a Luteinizing Hormone-Releasing Hormone Analog and Tamoxifen on the Growth of an Estrogen-Induced Prolactin-Secreting Rat Pituitary Tumor and Its Influence on Pituitary Gonadotropins*

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Abstract
The effect of a potent LHRH analog (ICI 118,630) on the growth of the estrogen-induced transplantable PRL-secreting rat pituitary tumor 7315a was compared with the effect of the antiestrogen tamoxifen. Implantation of this PRL-secreting tumor induced hyperprolactinemia, and plasma FSH and LH levels were suppressed. The total PRL content of the pituitary gland was decreased, but the glands of tumor-bearing animals contained 50–100% more FSH and LH than nontumor-bearing controls. Plasma 17β-estradiol concentrations and ovarian weight were not changed, but uterine weight decreased after tumor implantation. The administration of the LHRH analog (5 or 25 μg, sc, twice daily for 12 days) inhibited pituitary tumor growth by 68 ± 11% and 71 ± 8%, respectively (P < 0.01 and P < 0.01, respectively). This was accompanied by a decrease in plasma 17β-estradiol and the ovarian and uterine weights. The total FSH and LH contents of the pituitary glands of the LHRH-treated tumor-bearing rats were diminished in the presence of elevated circulating levels of FSH and LH 90 min after the last administration of the LHRH analog. A further dose-dependent inhibition of the total PRL content of the host's pituitary gland was observed after LHRH. The administration of tamoxifen (200 μg/kg- day) sc for 12 days inhibited tumor growth by 74 ± 6% (P < 0.01). After this treatment, plasma 17β-estradiol, ovarian and uterine weights, plasma FSH and LH, and the total pituitary content of PRL, FSH, and LH were not different from those in rats with control tumors. It is suggested that tamoxifen and the LHRH analog inhibit tumor growth in the model of the estrogen-induced transplantable rat pituitary tumor in different ways. Tamoxifen exerts its effects through a blockade of the estrogen receptors on the tumor, while LHRH induces a chemical castration despite a stimulating effect oh pituitary FSH and LH secretion. The strong tumor growth-inhibiting effect of this LHRH analog could have a practical application in the treatment of metastatic breast cancer and gonadal tumors in man. (Endocrinology108: 1878, 1981)