Circadian ACTH 1-17 effects on murine tritiated thymidine incorporation into DNA of thymus, bone marrow and spleen; also on total splenic RNA and DNA

Abstract

The importance of administration time along the 24-h scale is shown for a potent corticosteroidogenic adrenocorticotropin analogue, ACTH 1-17 (Synchrodyn 1-17). This molecule affects the incorporation of [3H]TdR into DNA (DNA synthesis) in the thymus, bone marrow and spleen, and total RNA and DNA of spleen in CD2F1 mice, standardized in light alternating with darkness at 12-h intervals. As a function of timing, the same dose of ACTH 1-17 at one time increases, at another time decreases (in each case with statistical significance) and at still another time elicits no response in DNA synthesis or in total RNA and DNA of spleen. Effects upon DNA synthesis are recorded with doses of 0.02 IU/kg body weight. The most marked effect with 20 IU/kg body weight is a decrease of DNA synthesis seen (4 h) after administration of ACTH 1-17 late in the dark span and early in the light span. The effect of ACTH 1-17 on the thymus is more prominent than that on bone marrow and spleen. Time-dependence also characterizes placebo effects by comparison to values in untreated controls. At the cellular level responses to ACTH 1-17 or placebo are characterized by critical interactions of treatment kind with treatment timing as well as interval-to-kill-time. The study documents the need to time-specify, in several ways, responses to ACTH 1-17 and suggests more broadly that 'increases' and 'decreases' may have to be complemented by changes in endpoints of rhythms in all those endocrine studies that involve rhythmic variables and rhythm-dependent effects upon these variables.