PMID- 33867395 OWN - NLM STAT- MEDLINE DCOM- 20220120 LR - 20220120 IS - 1348-4540 (Electronic) IS - 0918-8959 (Linking) VI - 68 IP - 8 DP - 2021 Aug 28 TI - Reduction of arcuate kappa-opioid receptor-expressing cells increased luteinizing hormone pulse frequency in female rats. PG - 933-941 LID - 10.1507/endocrj.EJ20-0832 [doi] AB - The brain mechanism responsible for the pulsatile secretion of gonadotropin-releasing hormone (GnRH) is important for maintaining reproductive function in mammals. Accumulating evidence suggests that kisspeptin/neurokinin B/dynorphin A (KNDy) neurons in the hypothalamic arcuate nucleus (ARC) play a critical role in the regulation of pulsatile GnRH and subsequent gonadotropin secretion. Dynorphin A (Dyn) and its receptor, kappa-opioid receptor (KOR, encoded by Oprk1), have been shown to be involved in the suppression of pulsatile GnRH/luteinizing hormone (LH) release. On the other hand, it is still unclear whether the inhibitory Dyn signaling affects KNDy neurons or KOR-expressing non-KNDy cells in the ARC or other brain regions. We therefore aimed to clarify the role of ARC-specific Dyn-KOR signaling in the regulation of pulsatile GnRH/LH release by the ARC specific cell deletion of KOR-expressing cells using Dyn-conjugated-saporin (Dyn-SAP). Estrogen-primed ovariectomized female rats were administered Dyn-SAP to the ARC. In situ hybridization of Oprk1 showed that ARC Dyn-SAP administration significantly decreased the number of Oprk1-expressing cells in the ARC, but not in the ventromedial hypothalamic nucleus and paraventricular nucleus. The frequency of LH pulses significantly increased in animals bearing the ARC Dyn-SAP administration. The number of Kiss1-expressing cells in the ARC was not affected by ARC Dyn-SAP treatment. Dyn-KOR signaling within the ARC seems to mediate the suppression of the frequency of pulsatile GnRH/LH release, and ARC non-KNDy KOR neurons may be involved in the mechanism modulating GnRH/LH pulse generation. FAU - Dai, Mingdao AU - Dai M AD - Laboratory of Theriogenology, Department of Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, Japan. FAU - Nakamura, Sho AU - Nakamura S AD - Laboratory of Theriogenology, Department of Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, Japan. FAU - Takahashi, Chudai AU - Takahashi C AD - Laboratory of Theriogenology, Department of Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, Japan. FAU - Sato, Marimo AU - Sato M AD - Laboratory of Theriogenology, Department of Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, Japan. FAU - Munetomo, Arisa AU - Munetomo A AD - Laboratory of Theriogenology, Department of Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, Japan. FAU - Magata, Fumie AU - Magata F AD - Laboratory of Theriogenology, Department of Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, Japan. FAU - Uenoyama, Yoshihisa AU - Uenoyama Y AD - Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan. FAU - Tsukamura, Hiroko AU - Tsukamura H AD - Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan. FAU - Matsuda, Fuko AU - Matsuda F AD - Laboratory of Theriogenology, Department of Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, Japan. LA - eng PT - Journal Article DEP - 20210417 PL - Japan TA - Endocr J JT - Endocrine journal JID - 9313485 RN - 0 (Receptors, Opioid, kappa) RN - 0 (Saponins) RN - 74913-18-1 (Dynorphins) RN - 9002-67-9 (Luteinizing Hormone) SB - IM MH - Animals MH - Arcuate Nucleus of Hypothalamus/drug effects/*metabolism MH - Dynorphins/administration & dosage MH - Female MH - Luteinizing Hormone/*blood MH - Neurons/drug effects/*metabolism MH - Rats MH - Rats, Wistar MH - Receptors, Opioid, kappa/*metabolism MH - Saponins/administration & dosage OTO - NOTNLM OT - Dynorphin OT - Kappa-opioid receptor OT - Kisspeptin/neurokinin B/dynorphin A neuron OT - Luteinizing hormone pulse OT - Saporin EDAT- 2021/04/20 06:00 MHDA- 2022/01/21 06:00 CRDT- 2021/04/19 06:10 PHST- 2021/04/20 06:00 [pubmed] PHST- 2022/01/21 06:00 [medline] PHST- 2021/04/19 06:10 [entrez] AID - 10.1507/endocrj.EJ20-0832 [doi] PST - ppublish SO - Endocr J. 2021 Aug 28;68(8):933-941. doi: 10.1507/endocrj.EJ20-0832. Epub 2021 Apr 17.