GH participates in the regulation of the expression of several hepatic proteins, some of which are subject to multihormonal control. We have previously shown the participation of glucocorticoids and thyroid hormones in the regulation of the hepatic low affinity glucocorticoid-binding sites (LAGS). Here, we provide evidence that also implicates GH in the endocrine control of the LAGS through the use of several animal models, all of them having a very low or undetectable plasma GH level: the hypothyroid (TX), the hypophysectomized, and the GH-deficient Lewis-derived dwarf rat. In dwarf rats, the level of LAGS was only 35% of that found in normal Lewis rats. Treatment of these rats with human (h) GH significantly increased the LAGS level in a dose-response manner. In TX rats, hGH treatment provoked a significant increase in the LAGS level (from 0.9 +/- 0.2 to 7.2 +/- 0.8 pmol/mg protein), so that it represented about 65% of the level found in intact animals. In both hypothyroid-adrenalectomized and hypophysectomized rats, the isolated effect of hGH was not as pronounced as in TX or dwarf rats; however, a potentiation of the effect of hGH was observed when this hormone was injected together with corticosterone acetate. On the other hand, when hGH, T3, and corticosterone acetate were given in combination to hypophysectomized rats, hGH and T3 behaved as agonists of the LAGS induction at T3 doses lower than or equal to 0.1 microgram/100 g BW and as antagonists at T3 doses higher than this. When T4 was used instead of T3, this hormone was capable of potentiating the effect of hGH at doses lower than or equal to 1.5 micrograms/100 g BW. From these results we conclude that 1) GH as well as thyroid and glucocorticoid hormones participate in the endocrine regulation of the LAGS; and 2) under physiological conditions, it is conceivable that GH, thyroid hormones, and glucocorticoids act synergistically in the endocrine regulation of the LAGS.