Simulation of peak pineal melatonin release restores sensitivity to evening melatonin injections in pinealectomized hamsters.

In intact hamsters held on LD 14:10, pineal melatonin production and release peaks late in the evening. If these animals receive a daily injection of melatonin approximately 8 h before the endogenous peak (at the time of lights out), they respond with testicular regression. Pinealectomized hamsters receiving only this evening injection do not respond. The hypothesis tested here is very simple: replacement of the pineal melatonin rhythm in pinealectomized hamsters with a daily melatonin injection at the time of peak melatonin release in intact hamsters should reestablish sensitivity to evening (lights out) injections of melatonin. Conversely, melatonin replacement at times other than this should be ineffective. Pinealectomized hamsters maintained on LD 14:10 (lights 0600 - 2000 h) were injected with melatonin (15 microgram) at the time of the endogenous melatonin peak (2 h prior to lights on) and in the evening (0.5 h prior to lights out). This injection paradigm produced a rapid testicular regression that appears to be dependent on the timing of melatonin injections with respect to the animal's circadian system. Two daily injections given with the same frequency (8.5 h apart) but during a different time of the day were not effective. The results suggest that rhythmic sensitivity to melatonin is not affected by removal of the pineal, and that this gland serves as the source of endogenous melatonin, which must be present at the proper time for exogenous injections of melatonin to produce testicular regression.