Mechanism of Triparanol-Induced Adrenal Hypertrophy and Reduced Adrenal Function

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Abstract
Triparanol at 0.03% in the diet was fed to intact and hypophysectomized rats for 35 days. In intact rats, triparanol decreased the sterol concentration in plasma, liver and adrenal glands. In addition, adrenal weights were increased and corticosterone concentrations in response to ACTH were reduced in both adrenal venous effluent and adrenal glands. The simultaneous feeding of cholesterol and cholic acid prevented the triparanol- induced sterol depletion, adrenal enlargement and reduced corticosterone concentrations in response to ACTH. Although triparanol reduced adrenal sterol in the hypophysectomized rat, there was no adrenal enlargement. It was concluded that adrenal enlargement and related impaired adrenal function caused by triparanol in the intact rat was primarily due to adrenal sterol depletion. It was suggested that, with a reduction in adrenal substrate, steroid synthesis is decreased. Therefore, to meet the need for adrenal steroids, the pituitary is activated to release adrenocorticotrophic hormone which stimulates the adrenal glands to increase corticoid production and ensuing adrenal enlargement. In the hypophysectomized animal, removal of the trophic hormone eliminates the pituitaryadrenal feedback mechanism, so that the adrenals are no longer stimulated and therefore do not enlarge.