Kinetic changes of melatonin release in rat pineal perifusions at different circadian stages. Effects of corticosteroids

The kinetic characteristics of melatonin release were documented in perifused pineal glands removed from rats sacrificed at six circadian stages (light/dark =12:12): three during the light phase, i.e. 3, 7 and 11 hours after light onset (HALO), and three during the dark phase, i.e. 15, 19 and 23 HALO. Whatever the circadian stage, the melatonin release decreased during the first 3–4 h and then remained fairly constant and roughly similar up to 8 h of perifusion. However, the kinetics of the release in the first 3 h differed in perifusions of pineal glands removed during the light (progressive decline during 3 h) as compared to perifusions of pineal glands removed during the dark (sharp decline during the first hour and then a progressive decline until reaching a constant level after 3 h). As the effects of steroid administration on melatonin secretion are a matter of controversy, we also studied the direct effects and their circadian stage dependence, if any, of corticosterone, deoxycorticosterone and dexamethasone on melatonin secretion by pineal glands removed 7 HALO (about the middle of the light phase) and 19 HALO (about the middle of the dark phase). High concentrations of corticosterone (0.8 × 10 −1 mol/l) and dexamethasone (0.4×10 −3 mol/l) resulted in a significant (p<0.001) inhibitory effect on melatonin production (about a 50% and a 30% decrease, respectively) whatever the circadian stage, whereas lower concentrations (10 −4 –10 −5 mol/l of both steroids did not affect melatonin production. In addition, neither pharmacological (1.06 × 10 −5 mol/l) nor physiological (for the rat) concentrations (2.1 × 10 −7 mol/l) of deoxycorticosterone had any significant effect on pineal melatonin production. These data clearly show the time dependence of the kinetics of melatonin release and an effect of adrenocortical steroids on pineal melatonin production that may be quite different according to the steroid and dosage.