The metabolism of [4 14C]4 androstene 3,17 dione and [4 14C]5α androstane 3α,17β diol were studied in the microsomal fraction and the metabolism of [4 14C]4 androstene 3,17 dione was studied in the 10,500 g supernatant fraction of liver from adult male rats castrated at birth or at 14 days of age. Some of these rats were adrenalectomized 6 wk after castration and given dexamethasone substitution for 14 consecutive days and some were not adrenalectomized and were treated with adrenocorticotrophin for 14 days. Untreated, castrated control rats were also investigated. Adrenalectomy combined with dexamethasone substitution abolished the masculine, imprinted character of the activities of 16α hydroxylase, 17α and 17β hydroxysteroid reductases and 5β reductase active on 4 androstene 3,17 dione and 2α and 2β hydroxylases active on 5α androstane 3α,17β diol in liver from male rats castrated at 14 days of age. The type of androgenic regulation characterizing these enzymes was called 'less stable' imprinting. In contrast to these findings, the activities of 5α reductase and 3β hydroxysteroid reductase retained their masculine character in male rats castrated 14 days after birth even after adrenalectomy combined with glucocorticoid substitution. The type of programming regulating these enzyme activities was called 'more stable' imprinting. 'Less stable' imprinting could be explained by the increased androgen responsiveness of the neonatally androgenized liver which thus responds more promptly to the enzyme inducing or suppressing effects of adrenal androgens. Adrenalectomy combined with dexamethasone substitition results in elimination of these effectors and consequently loss of the masculine character of the enzyme activities regulated by 'less stable' imprinting. The activity of 5β reductase, however, is regulated by unknown central factors. 'More stable' imprinting may be explained by a specific, autonomous, irreversible enzyme induction in liver independent of postpubertal hormonal stimuli. Corticotrophin treatment generally led to similar but less significant effects upon the hepatic enzyme activities than adrenalectomy combined with dexamethasone substitution. It is speculated that these effects may be attributable to increased glucocorticoid levels in blood possibly through secondary effects on central control mechanism(s) regulating hepatic enzyme activities.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism