Effects of Season and Estradiol on KNDy Neuron Peptides, Colocalization With D2 Dopamine Receptors, and Dopaminergic Inputs in the Ewe.
Seasonal reproduction in sheep is primarily due to a dramatic increase in the ability of estradiol (E2) to inhibit the pulsatile secretion of gonadotropin-releasing hormone (GnRH) during the nonbreeding season [anestrus (ANS)]. Recent findings suggest that kisspeptin/neurokinin B/dynorphin (KNDy) neurons of the arcuate nucleus (ARC) play a key role in conveying this negative feedback influence, with dopaminergic projections from the retrochiasmatic area acting upon KNDy cells to decrease kisspeptin release and thus inhibit GnRH pulses. However, several questions remain unanswered: (1) Are the coexpressed KNDy peptides, neurokinin B (NKB) and dynorphin, under seasonal regulation similar to kisspeptin? (2) Are seasonal changes in these peptides and their colocalization of D2 dopamine receptors (D2Rs) steroid dependent? and (3) Do KNDy neurons receive direct input from dopaminergic terminals? We used dual- and triple-label immunofluorescence to analyze brain sections through the ARC of ovariectomized (OVX) and OVX plus E2 ewes perfused during either the breeding season or ANS. Results showed (1) steroid-dependent and steroid-independent seasonal changes in kisspeptin and NKB, but not dynorphin, immunoreactivity; (2) increased D2R coexpression during ANS that was dependent on the presence of E2; and (3) evidence that KNDy cells receive direct contact from dopaminergic terminals and that this input increases during ANS. These results support the hypothesis that dopamine acts to inhibit GnRH secretion in ANS by directly suppressing the activity of ARC KNDy neurons, and implicate NKB as well as kisspeptin in seasonal shifts in E2-negative feedback in the sheep.
Neuroscience Graduate Program, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, USA.
Peyton
P
Weems
School of Anatomy, Physiology and Human Biology, The University of Western Australia, Nedlands, Western Australia, Australia.
Jeremy
J
Smith
Department of Physiology, Monash University, Clayton, Victoria, Australia.
Iain J
IJ
Clarke
Departments of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, USA.
Lique M
LM
Coolen
Department of Physiology and Pharmacology, West Virginia University, Morgantown, West Virginia.
Robert L
RL
Goodman
Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi.
Michael N
MN
Lehman
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism*; D004399:Dynorphins / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D059648:Kisspeptins / Q000378:metabolism*; D015287:Neurokinin B / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010052:Ovariectomy; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012098:Reproduction / Q000187:drug effects / Q000502:physiology; D012621:Seasons; D012756:Sheep
D059648:Kisspeptins; D017448:Receptors, Dopamine D2; D004958:Estradiol; D004399:Dynorphins; D015287:Neurokinin B