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• W2079889654 abstract "Exogenous corticosterone (B), the natural glucocorticoid product of rats, suppressed endogenous B production of isolated rat adrenocortical cells induced by αACTH-(l–24), [9-tryptophan (O-nitrophenylsulfenyl)]ACTH-(l–24) ([Trp (Nps)9]ACTH-(l–24)), and cAMP as well as pregnenolone supported- steroidogenesis. This self-suppression occurred within 2 h. It was dependent on the concentration of exogenous B. However, self-suppression did not alter the half-maximal steroidogenic concentration (ED50) of each steroidogenic agent. In addition, exogenous B did not suppress ACTH-induced cAMP production or gross protein synthesis, as measured by leucine incorporation into bulk cellular proteins. These results with isolated cells suggested at least two mechanisms for self-suppression: 1) exogenous B inhibited steroidogenic steps in a noncompetitive manner, and/or 2) exogenous B induced B degradation. In this study we examined the effect of exogenous B on the degradation of B. Accordingly, we measured the adrenal 5α-reductase activity (5αRA) of cell homogenates prepared from treated cells. Isolated adrenocortical cells were incubated for 2 h with aACTH-(l–24), ovine PRL (oPRL), and B. They were then homogenized and assayed for 5αRA, as indicated by the disappearance of exogenous B, as shown by RIA. In addition, the percentage of exogenous tritium-labeled B ([3H]B) converted to 5a-dihydrocorticosterone (DHB), the principal reduced metabolite of B, was determined by TLC. Isolated adrenocortical cells from intact rats showed insignificant 5αRA and DHB formation when incubated with or without aACTH- (1–24) and with or without oPRL. However, with exogenous B, there was significant 5αRA and DHB formation. oPRL plus B decreased DHB formation. The effects of B and oPRL were more demonstrable with cells from hypophysectomized rats. These cells exhibited high 5αRA and DHB formation; exogenous B increased these values, whereas oPRL acutely reversed the effects of hypophysectomy and exogenous B. In other work avoiding cell homogenization, exogenous B suppressed ACTHinduced B accumulation and increased DHB formation in intact cell suspensions from intact rats and intact male domestic fowl. Furthermore, exogenous B increased the conversion of [3H] pregnenolone to DHB in intact cell suspensions from intact rats, showing that B synthesized de novo as well as exogenous B can be degraded during self-suppression. These data indicate that acute self-suppression of corticosteroidogenesis is at least partly mediated by an increase in 5αRA. (Endocrinology115: 2464–2472,1984)" @default.
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• W2079889654 date "1984-12-01" @default.
• W2079889654 modified "2023-10-18" @default.
• W2079889654 title "Self-Suppression of Corticosteroidogenesis: Evidence for a Role of Adrenal 5α-Reductase*" @default.
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• W2079889654 doi "https://doi.org/10.1210/endo-115-6-2464" @default.
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