Effects of metyrapone and etomidate on adrenal function and growth rate in female rats

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Abstract
Two inhibitors of adrenal steroidogenesis were examined to determine whether the growth rate of female rats could be improved by lowering circulating plasma corticosterone concentrations. The first inhibitor, etomidate, is a potent narcotic agent and was found to have no effect on plasma corticosterone and deoxycorticosterone (DOC) concentrations at sub-narcotic doses. Growth rate, food intake, food conversion efficiency and adrenal weight were also unaffected by the drug. The second inhibitor, metyrapone, was shown in acute studies to have two distinct actions. In 6-week-old female rats moderate doses of metyrapone (50 mg/kg) had a stimulatory action resulting in increased plasma DOC and corticosterone concentrations. Higher doses of metyrapone (150–300 mg/kg) were increasingly less selective, causing an increase in plasma concentration of DOC, but attenuating the increase in corticosterone concentration, presumably by inhibiting the 11β-hydroxylase enzyme which allows the conversion of DOC to corticosterone. In adult rats (>12 weeks old) the classical response to metyrapone was observed. Plasma DOC concentrations were increased, while corticosterone levels were reduced in a dose-dependent manner. In 5-week-old rats treated chronically, metyrapone (300 mg/kg) had no effect on plasma corticosterone, but increased plasma DOC concentration, depressed food intake and reduced growth rate. In 8-week-old rats treated chronically, the high dose of metyrapone (300 mg/kg) required to lower peak plasma corticosterone concentrations produced toxic effects resulting in the death of three animals. The remaining animals recovered rapidly, and gained more weight than controls over the final 6 days of the experiment. However, this experiment was terminated before the treated animals were able to catch up with the controls. Inverse correlations were found between both plasma corticosterone and DOC concentrations and growth rate, confirming that growth may be retarded by the glucocorticoids and that inhibition of their production may be of potential use in stimulating growth. Neither of the agents tested in the present study, however, are likely to be future candidates as growth promoters. J. Endocr. (1987) 113, 473–478