Study of the Hormonal Control of Body and Organ Size in Rats with Mammotropic Tumors

Abstract

Rats bearing large transplantable pituitary tumors (MtT) have high blood levels of prolactin, growth hormone and ACTH, which produce large mammary glands, accelerated body growth with splanchnomegaly, atrophy of the pituitary gland and ovaries to weights of less than 50 % of normal and virtual disappearance of the thymus and of body (white) fat. Adrenal weight, which increased 8-fold, was found to be correlated directly with the weight of the kidney, and with the logarithm of the weight of the liver and of the heart. All organ weights are expressed as a function of body weight. When rats with MtT were thyroidectomized, tumor growth was retarded; body and gut length and the weights of the body, spleen and preputial gland remained normal; the increased weights of the liver and kidney were reduced toward normal; the reduced weights of the pituitary, ovary and white fat were increased toward normal. The effects of the hormones from the tumor were present but were quantitatively altered by the absence of thyroid hormone. Hence, the size of each of these tissues is partly controlled by hormones from the thyroid. Replacement therapy with thyroxine (10 μg/day) completely reversed the effects of thyroidectomy. When MtT-bearing rats were adrenalectomized, the weights of the mammary gland, liver, kidney, heart, empty gut and brown fat were markedly decreased, while the weights of the body, the thymus, preputial glands, pituitary gland and ovary were increased. Hence, the relative size of these tissues is partly controlled by hormones from the adrenal gland. The splanchnomegalic effects of the hormones from the tumor on these major organs were nullified by adrenalectomy, but the effect on body weight was not. When adrenalectomized rats having MtT could be kept alive on saline and occasional corticoid treatment, they rapidly grew to be giants with a body weight more than double that of normal animals but with major organs having only a normal proportion to body weight. This acceleration of body weight suggests that the adrenal gland is an important regulator of ultimate body size. Treatment of adrenalectomized rats with various corticoids even at high dosages did not reverse appreciably the effects of adrenal removal and did not cause splanchnomegaly. This suggests the presence in the secretions of the adrenal gland of some unknown factor which can produce splanchnomegaly of the kidney, liver and heart. The levels of prolactin, GH and ACTH in the blood and tumors of the thyroidectomized and adrenalectomized rats with MtT were not sufficiently different from the levels in intact rats with MtT to account for the changes in organ sizes, which are thought to reflect specific interactions with the hormones from the thyroid and the adrenal. The importance of a balance of the 4 pituitary hormones, i.e., prolactin, GH, ACTH and TSH, for normal body and organ growth in the intact animal is emphasized. (Endocrinology75: 670, 1964)