Studies to elucidate the thyroid hormone dependence of morris hepatoma 44

Authors

  • Raphael Pollack,

    1. Department of Medicine, Royal Victoria Hospital and McGill University Clinic, Montreal, Quebec H3A 1A1, Canada
    2. Departments of Biochemistry, Howard University, School of Medicine, Washington, D.C. 20059
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    • Dr. Pollack is the recipient of a Canadian Society for Clinical Investigation Student Research Award for this work.

  • Shaindel Y. Mishkin,

    1. Department of Medicine, Royal Victoria Hospital and McGill University Clinic, Montreal, Quebec H3A 1A1, Canada
    2. Departments of Biochemistry, Howard University, School of Medicine, Washington, D.C. 20059
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  • Harold P. Morris,

    1. Department of Medicine, Royal Victoria Hospital and McGill University Clinic, Montreal, Quebec H3A 1A1, Canada
    2. Departments of Biochemistry, Howard University, School of Medicine, Washington, D.C. 20059
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  • Mordechai A. Yalovsky,

    1. Department of Medicine, Royal Victoria Hospital and McGill University Clinic, Montreal, Quebec H3A 1A1, Canada
    2. Departments of Biochemistry, Howard University, School of Medicine, Washington, D.C. 20059
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  • Seymour Mishkin

    Corresponding author
    1. Department of Medicine, Royal Victoria Hospital and McGill University Clinic, Montreal, Quebec H3A 1A1, Canada
    2. Departments of Biochemistry, Howard University, School of Medicine, Washington, D.C. 20059
    • Division of Gastroenterology, Royal Victoria Hospital, Pine Avenue West, Montreal, Quebec, Canada H3A 1A1
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    • Dr. Mishkin is the recipient of a Chercheur Boursier of the Quebec Medical Research Council.


Abstract

The objective of these studies was to elucidate further the mechanisms of the thyroid dependency of Morris Hepatoma 44. In vivo experiments indicated that while exogenous thyroxine (8 μg per kg) reversed the hypothyroid-mediated inhibition of primary hepatoma growth, no such effect was noted with the administration of ovine prolactin (100 μg per kg s.c.) and bovine growth hormone (100 μg per kg, s.c). In contrast, ovine prolactin significantly stimulated tumor growth in euthyroid animals. We have documented the presence of nuclear triiodothyronine (T3) receptors in Morris Hepatoma 44. The dissociation constant Kd (4.38 ± 0.84 uM) and binding capacity (2.16 ± 0.84 pmoles per mg DNA) of these receptors was significantly greater than those of host liver tissue (1.48 ± 0.41 nM and 0.93 ± 0.32 pmole per mg DNA, respectively). The binding capacity of hepatoma nuclear T3 receptors was markedly reduced in the hypothyroid state, while liver nuclear receptor capacity was not significantly changed. In addition, the binding of T3 to cytoplasmic proteins was greater in hepatomas relative to host liver. Analogous to the observations with nuclear receptors, the binding of T3 to hepatoma cytosol was significantly reduced in the hypothyroid state, while the binding activity of liver cytosol was unchanged. These results are consistent with a possible role for nuclear receptors and/or cytoplasmic binding proteins for T3 in mediating the direct influence of thyroid hormones on the growth of Morris Hepatoma 44. Our results, however, do not preclude a role for other hormones (i.e., pituitary hormones acting via the hypothalamo-hypophyseal axis) as modulators of Morris Hepatoma 44 growth.

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