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Paradoxical Induction of Tyrosine Aminotransferase by Progesterone in Vivo: Potentiation of Effects of Low Levels of Glucocorticoid Hormone

Summary Progesterone, a steroid hormone with well-defined antiglucocorticoid properties in vitro, is shown, paradoxically, to be a potent inducer of hepatic tyrosine aminotransferase in normal but not in adrenalectomized rats. It is further shown that progesterone, in adrenalectomized animals, markedly potentiates the induction of TAT by low doses of hydrocortisone, but that this synergism disappears at high doses of the latter hormone. In contrast, there is no synergism between progesterone and the synthetic steroid dexamethasone, which, unlike both hydrocortisone and the natural endogenous glucocorticoid corticosterone, does not bind to transcortin. These observations suggest that both the induction of TAT in the normal animal, as well as the potentiation of the inducing effects of low doses of exogenous hydrocortisone in the adrenalectomized animal, are attributable to the displacement by progesterone of endogenous corticosterone and exogenous hydrocortisone, respectively, from transcortin and the consequent rise in concentration of free circulating glucocorticoid. Although progesterone competes strongly with natural glucocorticoids for transcortin, it does so only weakly for the cytosolic glucocorticoid receptor. In contrast to its purely antiglucocorticoid effects in vitro, the effects of progesterone in the intact animal may thus reflect a balance between true antiglucocorticoid effects at the cytosol receptor level and other “glucocorticomimetic” effects due to a rise in free glucocorticoid level resulting from the displacement of endogenous glucocorticoid from plasma binding sites. This work was supported in part by United States Public Health Service Grant HD-05506 and by the Perkin Memorial Fund of The Presbyterian Hospital in the City of New York.