Closed-loop feedback control of the nyctohemeral rise in adrenocortical system function

We tested the hypothesis that the increase in adrenocortical system activity is controlled by an error signal generated by the difference between a central reference, or set point, value and some aspect of circulating corticosterone levels in rats maintained on a 12-h light, 12-h dark cycle. The test rats were treated with cyanoketone, an inhibitor that blocks conversion of pregnenolone to progesterone; control rats were treated with vehicle. Test and control rats were fitted with arterial cannulas and, after recovery, continuously collected blood was sampled for plasma corticosterone at 5-min intervals over 2-h periods at five times during the day. Samples were collected at the end of each period for plasma adrenocorticotropin (ACTH). Corticosterone and ACTH levels were similar in the two groups of rats at the nadir (0-2 h after lights-on) and at the peak (0-2 h after lights-off) of the diurnal rhythm. During the time of the maximal diurnal rise in corticosterone (8-10 and 10-12 h after lights-on), test rats had lower mean corticosterone and higher ACTH levels than controls. Infusion of 8 micrograms corticosterone during the 2 h before lights-out did not significantly elevate mean corticosterone levels but decreased end ACTH levels in test rats, whereas similar infusions in control rats resulted in decreased mean corticosterone levels and no change in end ACTH. We conclude that the nyctohemeral rise in ACTH is driven by an error signal resulting from the difference between a central set point value and some aspect of plasma corticosterone levels.