Cholecystokinin directly inhibits neuronal activity of primary gonadotropin-releasing hormone cells through cholecystokinin-1 receptor.
Pulsatile secretion of GnRH-1 regulates gonadotropin release from anterior pituitary and thus is essential for reproduction. The present study focused on the role of cholecystokinin (CCK) in the GnRH-1 system. CCK is a neuropeptide abundantly expressed in the brain, which is implicated in activation of female reproductive behaviors and release of anterior pituitary hormones. Using dual-label immunocytochemistry coupled to confocal analysis, GnRH-1 neurons in adult mouse brain were found to express CCK-1 receptors (CCK-1R), and CCK fibers were detected contacting GnRH-1 axons. To address the function of CCK on GnRH-1 neurons, calcium imaging was used to monitor patterns of activity of GnRH-1 neurons maintained in an in vitro system known to retain many characteristics of GnRH-1 cells in vivo. Endogenous receptors for CCK (CCK-1R and CCK-2R) were blocked with selective antagonists. Results indicate that CCK-1R but not CCK-2R antagonist treatment increased the number of calcium peaks/GnRH-1 cell, mean peak amplitude, and percentage of GnRH-1 cells displaying high activity. The increased activity in GnRH-1 neurons observed after application of CCK-1R antagonist was blocked by coincubation with exogenous CCK. This study provides evidence that CCK acts directly on GnRH-1 neurons to attenuate GnRH-1 neuronal activity via CCK-1R activation.
Giacobini
Paolo
P
Cellular and Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-3714, USA.
Wray
Susan
S
D000367:Age Factors; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D011247:Pregnancy; D011673:Pulsatile Flow; D043886:Receptor, Cholecystokinin A / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D043886:Receptor, Cholecystokinin A; D007987:Gonadotropin-Releasing Hormone; D002766:Cholecystokinin; D002118:Calcium