Evidence for RGS4 modulation of melatonin and thyrotrophin signalling pathways in the pars tuberalis
S M Dupré1, H Dardente, M J Birnie
1Faculty of Life Sciences, University of Manchester, Manchester, UK.
Journal of Neuroendocrinology
|June 1, 2011
Summary
Regulator of G-protein signalling 4 (RGS4) is a melatonin-responsive gene in the pituitary pars tuberalis. RGS4 modulates cyclic AMP (cAMP) signaling, impacting seasonal neuroendocrine function and photoperiodic responses.
Area of Science:
- Endocrinology
- Neuroscience
- Molecular Biology
Background:
- Melatonin, a pineal hormone, regulates seasonal functions via the MT1 receptor in the pituitary pars tuberalis (PT), inhibiting cAMP production.
- Thyroid-stimulating hormone (TSH) opposes melatonin by increasing cAMP via the TSH receptor (TSH-R).
- Cyclic AMP (cAMP) is central to both melatonin and TSH signaling pathways, influencing photoperiodic responses.
Purpose of the Study:
- To investigate the role of Regulator of G-protein signalling 4 (RGS4) in melatonin and TSH signaling within the PT.
- To determine if RGS4 expression is responsive to melatonin and photoperiod.
- To elucidate RGS4's impact on cAMP signaling pathways.
Main Methods:
- Assessed RGS4 gene expression in sheep PT under varying photoperiods and melatonin treatment.
- Utilized transient transfection in COS7 cells to study interactions between MT1, TSH-R, RGS4, and a cAMP-response element luciferase reporter (CRE-luc).
Main Results:
- RGS4 expression significantly increased (2.5-fold) with melatonin treatment and showed acute sensitivity to day length changes.
- In short days, RGS4 peaked nocturnally; in long days, its rise and fall were delayed.
- RGS4 attenuated the inhibitory effect of melatonin on TSH-stimulated cAMP signaling in a cellular model.
Conclusions:
- RGS4 is a melatonin-responsive gene in the PT, influenced by photoperiod.
- RGS4 plays a role in modulating the interplay between melatonin and TSH signaling pathways.
- RGS4 may contribute to the morning induction of cAMP-dependent gene expression, enhancing photoperiodic sensitivity.
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