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Influence of pinealectomy and long-term melatonin administration on GH-IGF-I axis function in male rats
Z Ostrowska1, B Kos-Kudla, E Swietochowska
1Department of Clinical Biochemistry, Silesian Medical Academy, Pl. Traugutta 2, 41-800 Zabrze, Zabrze, Poland. ozdrasiek@poczta.onet.pl
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.
Insights
The pineal gland influences growth hormone (GH) and insulin-like growth factor-I (IGF-I) circadian rhythms, with melatonin playing a key role. Exogenous melatonin's effects on the GH-IGF-I axis depend on the pineal gland's presence.
Area of Science:
- Endocrinology
- Chronobiology
- Neuroscience
Background:
- The interplay between the pineal gland, melatonin, and the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis is not fully understood.
- Melatonin's specific role in the circadian regulation of GH and IGF-I requires further elucidation.
Purpose of the Study:
- To investigate the influence of pinealectomy and long-term melatonin (MEL) administration on the circadian GH-IGF-I axis in male rats.
- To determine if the effects of exogenous MEL on the GH-IGF-I axis are dependent on the presence of the pineal gland.
Main Methods:
- Studies involved 192 male Wistar rats subjected to pinealectomy or sham operation.
- Half of the animals in each group received daily intraperitoneal melatonin (50 microg/100g b.m.) for 4 weeks.
- Blood samples were collected every 3 hours for radioimmunoassay (RIA) of MEL, GH, and IGF-I concentrations.
Main Results:
- Pinealectomy and exogenous MEL significantly altered endogenous MEL daily profiles and circadian oscillations of GH and IGF-I.
- GH rhythm was suppressed post-pinealectomy; exogenous MEL increased GH and IGF-I concentrations during the day.
- The effects of exogenous MEL on the GH-IGF-I axis were more pronounced in rats with an intact pineal gland.
Conclusions:
- The pineal gland modulates the circadian GH-IGF-I axis, with endogenous MEL concentrations playing a significant role.
- Melatonin administration post-pinealectomy only partially restored GH-IGF-I axis function, suggesting involvement of other pineal factors.
- The efficacy of exogenous MEL on the GH-IGF-I axis is pineal gland-dependent, possibly involving indirect or direct pineal gland interactions.