RRC ID 77412
著者 Nagae M, Yamada K, Enomoto Y, Kometani M, Tsuchida H, Panthee A, Nonogaki M, Matsunaga N, Takizawa M, Matsuzaki S, Hirabayashi M, Inoue N, Tsukamura H, Uenoyama Y.
タイトル Conditional Oprk1-dependent Kiss1 deletion in kisspeptin neurons caused estrogen-dependent LH pulse disruption and LH surge attenuation in female rats.
ジャーナル Sci Rep
Abstract The gonadotropin-releasing hormone (GnRH) pulse and surge are considered to be generated by arcuate kisspeptin/neurokinin B/dynorphin A (KNDy) neurons and anteroventral periventricular nucleus (AVPV) kisspeptin neurons, respectively, in female rodents. The majority of KNDy and AVPV kisspeptin neurons express κ-opioid receptors (KORs, encoded by Oprk1) in female rodents. Thus, this study aimed to investigate the effect of a conditional Oprk1-dependent Kiss1 deletion in kisspeptin neurons on the luteinizing hormone (LH) pulse/surge and fertility using Kiss1-floxed/Oprk1-Cre rats, in which Kiss1 was deleted in cells expressing or once expressed the Oprk1/Cre. The Kiss1-floxed/Oprk1-Cre female rats, with Kiss1 deleted in a majority of KNDy neurons, showed normal puberty while having a one-day longer estrous cycle and fewer pups than Kiss1-floxed controls. Notably, ovariectomized (OVX) Kiss1-floxed/Oprk1-Cre rats showed profound disruption of LH pulses in the presence of a diestrous level of estrogen but showed apparent LH pulses without estrogen treatment. Furthermore, Kiss1-floxed/Oprk1-Cre rats, with Kiss1 deleted in approximately half of AVPV kisspeptin neurons, showed a lower peak of the estrogen-induced LH surge than controls. These results suggest that arcuate and AVPV kisspeptin neurons expressing or having expressed Oprk1 have a role in maintaining normal GnRH pulse and surge generation, the normal length of the estrous cycle, and the normal offspring number in female rats.
巻・号 13(1)
ページ 20495
公開日 2023-11-22
DOI 10.1038/s41598-023-47222-5
PII 10.1038/s41598-023-47222-5
PMID 37993510
PMC PMC10665460
MeSH Animals Arcuate Nucleus of Hypothalamus / metabolism Dynorphins / metabolism Estrogens / pharmacology Female Gonadotropin-Releasing Hormone / metabolism Kisspeptins* / metabolism Luteinizing Hormone* / pharmacology Neurokinin B / genetics Neurokinin B / metabolism Neurons / metabolism Rats
IF 3.998
リソース情報
ラット LE-Tg(Gt(ROSA)26Sor-CAG-tdTomato)24Jfhy (StrainID=1139)