Response of adrenal 3β-hydroxy-Δ5-steroid dehydrogenase to adrenocorticotropin treatment in thiouracil-fed male mice

Abstract

A number of parallels can be drawn between the reported endocrine status of thiouracil-fed young rodents and that of aged animals, particularly with regard to the hypothalamus–pituitary–adrenal axis. Since the activity of the adrenal steroidogenic enzyme 3β-hydroxy-Δ5-steroid dehydrogenase (3β-HSD) has been shown to be depressed in aged rats and mice, the present study was done to determine whether exposure of young mice to thiouracil had a similar effect on adrenal 3β-HSD activity. Feeding the goitrogen thiouracil at 0.25% (w/w) of the maternal diet from conception, and keeping it 0.25% of the offsprings diet after weaning, significantly elevated activity of 3β-HSD per gram of adrenal gland above control levels in 4-month-old mice, perhaps to compensate for depressed adrenal mass. Daily subcutaneous injections of physiological saline (0.9%) for 4 days was sufficient to increase 3β-HSD activity per gram of adrenal tissue in euthyroid (P < 0.05) but not in thiouracil-fed mice. Subcutaneous administration of ACTH (2 IU daily for 4 days) significantly increased adrenal 3β-HSD activity to comparable levels in thiouracil-fed and euthyroid animals. Thus, thiouracil enhances the activity of 3β-HSD per gram of adrenal tissue and does not prevent response of enzyme activity to exogenous ACTH.