Conditional Oprk1-dependent Kiss1 deletion in kisspeptin neurons caused estrogen-dependent LH pulse disruption and LH surge attenuation in female rats

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 neuron...

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Published in:	Scientific reports Vol. 13; no. 1; p. 20495
Main Authors:	Nagae, Mayuko, Yamada, Koki, Enomoto, Yuki, Kometani, Mari, Tsuchida, Hitomi, Panthee, Arvinda, Nonogaki, Miku, Matsunaga, Nao, Takizawa, Marina, Matsuzaki, Sena, Hirabayashi, Masumi, Inoue, Naoko, Tsukamura, Hiroko, Uenoyama, Yoshihisa
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 22-11-2023 Nature Publishing Group Nature Portfolio
Subjects:	631/378 631/443/494 Animals Arcuate Nucleus of Hypothalamus - metabolism Dynorphin A Dynorphins - metabolism Estrogens Estrogens - pharmacology Estrus cycle Female Fertility Gonadotropin-releasing hormone Gonadotropin-Releasing Hormone - metabolism Gonadotropins Humanities and Social Sciences Kiss1 protein Kisspeptins - metabolism Luteinizing hormone Luteinizing Hormone - pharmacology multidisciplinary Neurokinin Neurokinin B Neurokinin B - genetics Neurokinin B - metabolism Neurons Neurons - metabolism Offspring Opioid receptors Ovariectomy Periventricular nucleus Pituitary (anterior) Puberty Rats Rodents Science Science (multidisciplinary)
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-023-47222-5