Desoxycorticosterone-Mimetic Action of Ammoniated Glycyrrhizin in Rats

Abstract

The desexycorticosterone-mimetic action of ammoniated glycyrrhizin on electrolyte and water metabolism and on pituitary-adrenal function, was demonstrated in rats. Retention of sodium and water was observed in both intact and adrenalectomized rats during 4 hour minerosteroid assays, the degree of retention being a function of log dose. In intact rats, the antidiuretic effect of glycyrrhizin was immediate and cumulative, while retention of sodium appeared only after a latent period and did not increase with time. Adrenalectomized rats, 3 days after the operation, showed a more marked antidiuretic effect than intact rats, but no greater retention of sodium. Rats receiving glycyrrhizin prior to histamine stress showed a marked decrease in adrenal ascorbic acid depletion, suggesting that glycyrrhizin had suppressed the output of ACTH. Whether glycyrrhizin acts on the same target organ as desoxycorticosterone in producing sodium and water retention is still an open question. However, the fact that it is capable of producing a pituitary-adrenal inhibition which resembles that of naturally occurring adrenal steroids is further evidence of the strong pharmacological resemblance between glycyrrhizin and desoxycorticosterone.

Glycyrrhizin-Induced Inhibition of the Pituitary-Adrenal Stress Response

“…Those treated with glycyrrhizin had a higher mortality and a diminished mobilization of glucose. These observations, coupled with the decrease in adrenal ascorbic acid response (10) and the atrophy of the adrenal cortex (12) observed in glycyrrhizin-treated animals, strongly suggest that glycyrrhizin depresses the output of ACTH.…”

“…Animals treated with glycyrrhizin develop adrenal cortical atrophy (12) and show less than normal reduction of adrenal ascorbic acid in response to histamine (10). In the present investigation two additional indices of pituitary-adrenal function, namely resistance to cold stress and capacity to mobilize glucose during fasting, were studied in normal and glycyrrhizin-treated animals.…”

“…Subsequently, both the active principle, glycyrrhizinic acid (3) and the crude extract have been shown capable of replacing desoxycorficosterone in treatment of patients with Addison's disease (3)(4)(5)(6)(7)(8) or with total adrenalectomy (9). Glycyrrhizin-induced retention of sodium and water has been demonstrated in both intact (10) and adrenalectomized (10,11) rats.…”

“…The action of glycyrrhizin further resembles that of desoxycorticosterone in its inhibitory effect on the pituitary-adrenal system (10,12). Animals treated with glycyrrhizin develop adrenal cortical atrophy (12) and show less than normal reduction of adrenal ascorbic acid in response to histamine (10).…”