Effects of hypophysectomy and hormone replacement on the local and metastatic growth of Morris hepatoma 44.

We have demonstrated recently that the local metastatic growth of Morris hepatoma 44 is thyroid dependent ( Mishkin , S., Morris, H. P., Yalovsky , M., and Murthy , P. V. N. Gastroenterology, 77; 547-555, 1979; Mishkin , S. Y., Pollack , R., Morris, H. P., Yalovsky , M., and Mishkin , S. Cancer Res., 41: 3040-3045, 1981) and that exogenous thyroxine (8 micrograms/kg/day) and prolactin (100 micrograms/day) significantly stimulated tumor growth, while growth hormone (100 micrograms/day) failed to do so ( Pollack , R., Mishkin , S. Y., Morris, H. P., and Mishkin , S. Hepatology, 2: 836-842, 1982). In the present study, thyroid ablation (hypothyroidism) and hypophysectomy inhibited tumor growth significantly. These effects were almost totally reversed by administration of exogenous thyroxine to hypothyroid rats. While prolactin or growth hormone or thyroxine alone failed to restore tumor growth in hypophysectomized animals, administration of all three hormones partially but significantly reversed the inhibition of tumor growth. The number and size of pulmonary metastases paralleled local growth in all the above-mentioned conditions. Plasma membrane lactogenic receptors, measured using human growth hormone, were decreased in hypothyroidism and hypophysectomy groups. Binding levels were restored in those groups in which tumor growth was stimulated. In summary, the local and metastatic growth of Morris hepatoma 44 is affected by anterior pituitary hormones. Plasma membrane lactogenic receptors may mediate these effects.