Influence of pinealectomy and long-term melatonin administration on GH-IGF-I axis function in male rats.

BACKGROUND: A relationship between circadian GH-IGF-I axis activity and pineal gland function in rats is not sufficiently elucidated, particularly in the aspect of melatonin (MEL) participation with relation to a possible mechanism of these dependencies.

OBJECTIVE: Influence of pinealectomy and long-term MEL administration on circadian GH-IGF-I axis function in male rats was evaluated. An attempt was also made to determine whether the effect of exogenous MEL is dependent on the pineal gland presence.

METHODS: Studies were performed in 192 sexually mature male Wistar rats, which were subjected to pinealectomy or sham operation. In half of the animals from each group MEL (Sigma, USA) in dose of 50 microg/ 100g b.m. was administrated intraperitoneally (daily between 5 and 6 pm during a 4-week period). Blood for RIA assays of MEL, GH and IGF-I concentrations was collected every 3 hours during a day-beginning at 8 am (rats killed by decapitation).

RESULTS: Significant influence of pinealectomy and exogenous MEL on a daily profile of endogenous MEL in rats was confirmed. Distinct, dependent on the time of the day anomalies in circadian oscillations of GH and IGF-I showing positive correlation with changes in endogenous MEL concentrations were also shown. GH rhythm was suppressed in a group of rats with removed pineal gland; after pinealectomy distinct decrease and after MEL use - distinct increase of GH and IGF-I concentrations during the day were observed. It had influenced mean daily concentrations and values of amplitude of circadian GH and IGF-I oscillations in all studied groups of animals. In rats with preserved pineal gland the effect of exogenous MEL action was more intensified.

CONCLUSIONS: Pineal gland can influence circadian function of GH-IGF-I axis, and in mechanism of this dependence, changes in endogenous MEL concentrations seem to play an important role. Administration of MEL in rats after pinealectomy only partly prevents changes of GH-IGF-I axis function caused by gland removal, which can indicate participation of other pineal gland substances in generating disturbances. Influence of exogenous MEL on GH-IGF-I axis function during the day is dependent on the presence of pineal gland, which can be connected with indirect and/or direct influence of administrated hormone on this gland.