PMID- 28324006 OWN - NLM STAT- MEDLINE DCOM- 20170428 LR - 20190418 IS - 1945-7170 (Electronic) IS - 0013-7227 (Print) IS - 0013-7227 (Linking) VI - 158 IP - 4 DP - 2017 Apr 1 TI - Effects of Season and Estradiol on KNDy Neuron Peptides, Colocalization With D2 Dopamine Receptors, and Dopaminergic Inputs in the Ewe. PG - 831-841 LID - 10.1210/en.2016-1830 [doi] AB - 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. CI - Copyright (c) 2017 Endocrine Society. FAU - Weems, Peyton AU - Weems P AD - Neuroscience Graduate Program, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, USA. FAU - Smith, Jeremy AU - Smith J AD - School of Anatomy, Physiology and Human Biology, The University of Western Australia, Nedlands, Western Australia, Australia. FAU - Clarke, Iain J AU - Clarke IJ AD - Department of Physiology, Monash University, Clayton, Victoria, Australia. FAU - Coolen, Lique M AU - Coolen LM AD - Departments of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, USA. FAU - Goodman, Robert L AU - Goodman RL AD - Department of Physiology and Pharmacology, West Virginia University, Morgantown, West Virginia. FAU - Lehman, Michael N AU - Lehman MN AD - Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi. LA - eng GR - R01 HD017864/HD/NICHD NIH HHS/United States GR - R01 HD039916/HD/NICHD NIH HHS/United States PT - Journal Article PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (Kisspeptins) RN - 0 (Receptors, Dopamine D2) RN - 4TI98Z838E (Estradiol) RN - 74913-18-1 (Dynorphins) RN - 86933-75-7 (Neurokinin B) SB - IM MH - Animals MH - Arcuate Nucleus of Hypothalamus/metabolism MH - Dopaminergic Neurons/*metabolism MH - Dynorphins/*metabolism MH - Estradiol/*pharmacology MH - Female MH - Kisspeptins/*metabolism MH - Neurokinin B/*metabolism MH - Neurons/*drug effects/metabolism MH - Ovariectomy MH - Receptors, Dopamine D2/*metabolism MH - Reproduction/drug effects/physiology MH - Seasons MH - Sheep PMC - PMC5460800 EDAT- 2017/03/23 06:00 MHDA- 2017/04/30 06:00 PMCR- 2018/04/01 CRDT- 2017/03/22 06:00 PHST- 2016/11/09 00:00 [received] PHST- 2017/01/11 00:00 [accepted] PHST- 2017/03/23 06:00 [pubmed] PHST- 2017/04/30 06:00 [medline] PHST- 2017/03/22 06:00 [entrez] PHST- 2018/04/01 00:00 [pmc-release] AID - 2908844 [pii] AID - endo_161830 [pii] AID - 10.1210/en.2016-1830 [doi] PST - ppublish SO - Endocrinology. 2017 Apr 1;158(4):831-841. doi: 10.1210/en.2016-1830.