Evidence for an increased secretory capacity for dehydroepiandrosterone-sulphate in the pantothenic acid-deficient rat associated with an impaired adrenal cholesterol deposition.

Abstract

The adrenal capacity to store cholesterol and to secrete corticosterone, androstenedione, and dehydroepiandrosterone-sulphate (DHEA-S) was investigated following long- and short-term adrenocor-ticotropic hormone (ACTH) stimulation of growing male rats kept on a pantothenic acid-deficient (PAD) diet for about two months. After chronic treatment with ACTH1-24, the pantothenic acid-deficient rats revealed a drastic impairment in adrenal cholesterol storage compared with ad libitum and pair-weight fed control groups. However, corticosteroid plasma responses to short-term as well as to prolonged ACTH stimulation were normal or in the case of DHEA-S, even significantly increased in pantothenic acid deficiency. The elevated secretory capacity for this androgen sulphate was also discernible in an exaggerated renal DHEA-S excretion in PAD rats under ACTH1-24 hyperstimulation. According to the results of a further hormonal study involving metyrapone administration, a PAD-associated increase in specific enzyme activities of the post-pregnenolone pathway of androgen synthesis was excluded as the reason for the DHEA-S hypersecretion. The experimental findings are discussed with regard to a PAD-induced tissue CoA decrease and its consequences for adrenal cholesterol metabolism and steroid hormone secretion. A concept is presented that takes into account the functional differences in the zona fasciculata and the zona reticularis of the adrenal cortex in order to explain the phenomenon of the abnormal capacity of rats to secrete DHEA-S in pantothenic acid deficiency.