Summary
The potency of various cyclic nucleotides and their respective butyryl derivatives to stimulate the synthesis of corticosterone was studied in rat adrenal slices.
For half-maximal stimulation of the synthesis a concentration of 6×10−5 M of DBA was required, while c-AMP and c-GMP were active in 50 and 170 times higher concentrations, respectively. Still higher concentrations were needed of c-IMP. c-UMP had no significant stimulatory effect in concentrations of up to 10−2 M. The butyryl derivatives of the cyclic nucleotides were active in half the concentrations (or less) required for the parent compounds.
Addition of AMP, GMP or IMP to the incubation medium showed a tendency to stimulate the synthesis of corticosterone, while UMP inhibited it. Adenosine, adenine and allopurinol, an inhibitor of xanthine oxidase, stimulated the synthesis of corticosterone, but their maximal effects were only about one tenth that of ACTH or c-AMP.
While inosine and hypoxanthine, but not xanthine, inhibited the basal synthesis of corticosterone, all three compounds increased the ACTH- or DBA-stimulated steroidogenesis. This phenomenon was most prominent, when the adrenal slices were preincubated with these purine derivatives for 30 min before ACTH or DBA were added.
It was shown that c-IMP and c-GMP are able to substitute for the second messenger, c-AMP, in corticosterone synthesis in vitro and that the accumulation of metabolites of the nucleotides may also affect steroidogenesis.
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Vapaatalo, H., Bieck, P. & Westermann, E. Actions of various cyclic nucleotides, nucleosides and purine bases on the synthesis of corticosterone in vitro. Naunyn-Schmiedeberg's Arch. Pharmacol. 275, 435–443 (1972). https://doi.org/10.1007/BF00501131
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DOI: https://doi.org/10.1007/BF00501131