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Melatonin inhibits GnRH-induced increase of cFOS immunoreactivity in neonatal rat pituitary
Abstract:
In neonatal rat gonadotrophs, melatonin inhibits several GnRH-induced effects: stimulation of LH release as well as the increase of several second messengers as cAMP, diacylglycerol and [Ca2+]i . Recently, GnRH has been shown to induce expression of immediate early genes of fos and jun family in adult rat gonadotrophs. The purpose of this study was to determine, whether melatonin inhibits the GnRH-induced induction of cFos in neonatal rat pituitary cells. The effects of GnRH and/or melatonin on cFos immunoreactivity was determined in primary cultures of neonatal rat pituitary cells attached to the coverslip. GnRH (3 nM) induced a time-dependent increase of cFos immunoreactivity in about 10 to 15% of the cultured cells. Significant increase was observed already 30 min after GnRH administration, the maximal increase occurred after about 60 min and then gradually decreased. Melatonin (100 nM) markedly attenuated the GnRH-induced increase. GnRH increased cFos immunoreactivity in the cells in a dose-dependent manner (EC50=36 pM) and melatonin (100 nM) attenuated the response at all GnRH concentrations tested. Melatonin had no effect on basal cFos immunoreactivity, but it inhibited the GnRH-induced (10 nM) increase of cFos in dose-dependent manner (EC50=12 pM). In conclusion, this is the first report showing the inhibitory effect of melatonin on gene transcriptional activity in gonadotrophs.
Insights
Melatonin inhibits gonadotropin-releasing hormone (GnRH)-induced c-Fos gene expression in neonatal rat pituitary cells. This study demonstrates melatonin
Area of Science:
- Endocrinology
- Neuroscience
- Molecular Biology
Background:
- Melatonin is known to inhibit gonadotropin-releasing hormone (GnRH)-induced effects in neonatal rat gonadotrophs, including luteinizing hormone (LH) release and second messenger signaling.
- Gonadotropin-releasing hormone (GnRH) induces the expression of immediate early genes, such as c-Fos and c-Jun, in adult rat gonadotrophs.
Purpose of the Study:
- To investigate whether melatonin inhibits the GnRH-induced induction of c-Fos expression in neonatal rat pituitary cells.
Main Methods:
- Primary cultures of neonatal rat pituitary cells were treated with GnRH and/or melatonin.
- c-Fos immunoreactivity was quantified to assess gene expression changes.
- Dose-response and time-course experiments were conducted to characterize the effects of GnRH and melatonin.
Main Results:
- GnRH (3 nM) induced a time-dependent increase in c-Fos immunoreactivity in 10-15% of cultured cells, with maximal induction at 60 minutes.
- Melatonin (100 nM) significantly attenuated the GnRH-induced increase in c-Fos immunoreactivity.
- Melatonin inhibited GnRH-induced c-Fos expression in a dose-dependent manner (EC50 = 12 pM), without affecting basal levels.
Conclusions:
- This study provides the first evidence that melatonin inhibits GnRH-induced gene transcriptional activity in neonatal rat gonadotrophs.
- Melatonin's inhibitory effect on c-Fos induction suggests a role in regulating GnRH signaling pathways during early development.