THE ROLE OF GROWTH-HORMONE IN REGULATION OF LOW-AFFINITY GLUCOCORTICOID-BINDING SITES FROM MALE-RAT LIVER-MICROSOMES

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 hor mones in the regulation of the hepatic low affinity glucocorticoid-bin ding sites (LAGS). Here, we provide evidence that also implicates GH i n 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-defficient Le wis-derived dwarf rat. In dwarf rats, the level of LAGS was only 35% o f that found in normal Lewis rats. Treatment of these rats with human (h) GH significantly increased the LAGS level in a dose-response manne r. In TX rats, hGH treatment provoked a significant increase in the LA GS 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 h ypothyroid-adrenalectomized and hypophysectomized rats, the isolated e ffect 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 i njected together with corticosterone acetate. On the other hand, when hGH, T-3, and corticosterone acetate were given in combination to hypo physectomized rats, hGH and T-3 behaved as agonists of the LAGS induct ion at T-3 doses lower than or equal to 0.1 mu g/100 g BW and as antag onists at T-3 doses higher than this. When T-4 was used instead of T-3 , this hormone was capable of potentiating the effect of hGH at doses lower than or equal to 1.5 mu g/100 g BW. From these results we conclu de that 1) GK as well as thyroid and glucocorticoid hormones participa te in the endocrine regulation of the LAGS; and 2) under physiological conditions, it is conceivable that GH, thyroid hormones, and glucocor ticoids act synergistically in the endocrine regulation of the LAGS.