Study of the role of adrenocortical cyclic AMP and cyclic GMP on ascorbic acid depletion and corticosteroidogenesis by analysis of circadian rhythms

Abstract

Abstract. cAMP, cGMP and ascorbic acid were each measured in the adrenal cortex of young adult male rats killed in groups of 8 animals at around 08.00, 12.00, 18.00, 20.00, 00.00 and 04.00. The animals had been synchronized with natural daylight (07.00–19.00) and darkness alternation for 2 weeks. Plasma corticosteroids were determined in blood samples collected at the time of killing. The results were analyzed by both conventional and cosinor statistical methods. The existence of circadian rhythms was confirmed with P < 0.005 for the four variables studied. The extreme values ranged between 65 ± 4.3 (sem) and 745 ± 101 nm for corticosterone, 9.06 ± 0.4 and 13.23 ± 0.92 pmol/mg protein for cAMP, 0.69 ± 0.05 and 1.6 ± 0.17 pmol/mg protein for cGMP and 147 ± 7 and 218 ± 16 nmol/mg protein for ascorbic acid. The estimated acrophases were located at ≅ 21.00 for plasma corticosterone, at ≅ 11.00 for adrenocortical ascorbic acid (the corresponding nadir being located at ≅ 23.00), at ≅ 01.00 for cAMP and at ≅ 07.00 for cGMP. Expressing the data as the ratio of cAMP to cGMP reveals a circadian variation with a 21.00 peak synchronous with the corticosterone acrophase and just preceding the ascorbic acid nadir. A highly significant (P < 0.001) increase in corticosterone and a less significant (P < 0.05) decrease in ascorbic acid occurred until 16.00, whereas the cAMP levels remained low and constant. During the same period the cGMP levels decreased very significantly (P < 0.001). These phase relationships suggest that under physiological conditions, the action of corticotropin for both corticosteroidogenesis and ascorbic acid depletion might be mediated by the relative concentrations of cAMP and cGMP.