Document Detail

Evidence that dopamine acts via kisspeptin to hold GnRH pulse frequency in check in anestrous ewes.
MedLine Citation:
PMID:  23038740     Owner:  NLM     Status:  MEDLINE    
Recent work has implicated stimulatory kisspeptin neurons in the arcuate nucleus (ARC) as important for seasonal changes in reproductive function in sheep, but earlier studies support a role for inhibitory A15 dopaminergic (DA) neurons in the suppression of GnRH (and LH) pulse frequency in the nonbreeding (anestrous) season. Because A15 neurons project to the ARC, we performed three experiments to test the hypothesis that A15 neurons act via ARC kisspeptin neurons to inhibit LH in anestrus: 1) we used dual immunocytochemistry to determine whether these ARC neurons contain D2 dopamine receptor (D2-R), the receptor responsible for inhibition of LH in anestrus; 2) we tested the ability of local administration of sulpiride, a D2-R antagonist, into the ARC to increase LH secretion in anestrus; and 3) we determined whether an antagonist to the kisspeptin receptor could block the increase in LH secretion induced by sulpiride in anestrus. In experiment 1, 40% of this ARC neuronal subpopulation contained D2-R in breeding season ewes, but this increased to approximately 80% in anestrus. In experiment 2, local microinjection of the two highest doses (10 and 50 nmol) of sulpiride into the ARC significantly increased LH pulse frequency to levels 3 times that seen with vehicle injections. Finally, intracerebroventricular infusion of a kisspeptin receptor antagonist completely blocked the increase in LH pulse frequency induced by systemic administration of sulpiride to anestrous ewes. These results support the hypothesis that DA acts to inhibit GnRH (and LH) secretion in anestrus by suppressing the activity of ARC kisspeptin neurons.
Robert L Goodman; Matthew J Maltby; Robert P Millar; Stanley M Hileman; Casey C Nestor; Brant Whited; Ashlie S Tseng; Lique M Coolen; Michael N Lehman
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-10-04
Journal Detail:
Title:  Endocrinology     Volume:  153     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-29     Completed Date:  2013-01-31     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5918-27     Citation Subset:  AIM; IM    
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MeSH Terms
Anestrus / drug effects
Dopamine / metabolism*
Gonadotropin-Releasing Hormone / metabolism*
Immunohistochemistry / methods
Kisspeptins / metabolism*
Luteinizing Hormone / metabolism
Models, Biological
Neurons / metabolism
Receptors, Dopamine D2 / metabolism
Grant Support
Reg. No./Substance:
0/Kisspeptins; 0/Receptors, Dopamine D2; 33515-09-2/Gonadotropin-Releasing Hormone; 9002-67-9/Luteinizing Hormone; VTD58H1Z2X/Dopamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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