Expression of the GABAA receptor associated protein Gec1 is circadian and dependent upon the cellular clock machinery in GnRH secreting GnV-3 cells.
The timely regulation of gonadotropin-releasing hormone (GnRH) secretion requires a GABAergic signal. We hypothesized that GEC1, a protein promoting the transport of GABA(A) receptors, could represent a circadian effector in GnRH neurons. First, we demonstrated that gec1 is co-expressed with the GABA(A) receptor in hypothalamic rat GnRH neurons. We also confirmed that the clock genes per1, cry1 and bmal1 are expressed and oscillate in GnRH secreting GnV-3 cells. Then we could show that gec1 is expressed in GnV-3 cells, and oscillates in a manner temporally related to the oscillations of the clock transcription factors. Furthermore, we could demonstrate that these oscillations depend upon Per1 expression. Finally, we observed that GABA(A) receptor levels at the GnV-3 cell membrane are timely modulated following serum shock. Together, these data demonstrate that gec1 expression is dependent upon the circadian clock machinery in GnRH-expressing neurons, and suggest for the first time that the level of GABA(A) receptor at the cell membrane may be under timely regulation. Overall, they provide a potential mechanism for the circadian regulation of GnRH secretion by GABA, and may also be relevant to the general understanding of circadian rhythms.
Mansuy
Virginie
V
Services of Endocrinology, Diabetology, and Metabolism of the University Hospital of Lausanne, Switzerland.
Risold
Pierre-Yves
PY
Glauser
Micheline
M
Fraichard
Annick
A
Pralong
François P
FP
D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics; D005576:Colforsin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006736:Horses; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D056950:Period Circadian Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D044967:Serum
D002352:Carrier Proteins; C530814:Gabarapl1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; C539024:Per1 protein, rat; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D005576:Colforsin; D007987:Gonadotropin-Releasing Hormone