Regulation of PACAP gene expression by ovarian sex steroids and kisspeptin: Study using hypothalamic cell lines and an in vivo female rat model
- 1Department of Obstetrics and Gynecology, Shimane University Faculty of Medicine, Izumo, 693-8501, Japan.
Abstract
Objective: We investigated the effects of sex steroid hormones on hypothalamic PACAP expression. In addition, the mutual interaction of PACAP and kisspeptin was examined using hypothalamic cell models and an in vivo rat model.
Materials and methods: The effects of estradiol (E2), progesterone (P4), and dihydrotestosterone (DHT) on PACAP gene expression was examined using the GT1-7, rHypoE-8, and mHypoA-55 cell lines. The effect of PACAP on Kiss-1 gene expression and the effect of kisspeptin on PACAP gene expression were also examined. In addition, PACAP and Kiss-1 gene expression in the hypothalamus was determined in ovariectomized (OVX) and ovary-intact rats with and without sex steroid hormone supplementation.
Results: PACAP gene expression was not modulated by E2 or P4 stimulation, but DHT stimulation slightly increased its expression in GT1-7, rHypoE-8, and mHypoA-55. Stimulation with 100 nM PACAP significantly increased Kiss-1 gene expression in all three hypothalamic cell lines. Similarly, stimulation with 100 nM kisspeptin-10 also increased PACAP gene expression. PACAP gene expression within the posterior part of the hypothalamus was increased after OVX, and the OVX-induced increase in PACAP gene expression was suppressed by supplementation with E2, P4, and DHT, showing a pattern similar to that observed for Kiss-1 gene expression. In ovary-intact female rats, E2 administration, but not P4 or DHT, reduced PACAP gene expression.
Conclusion: PACAP expression within the hypothalamus may not be regulated directly by E2 and P4. Although PACAP and kisspeptin mutually interact and regulate each other, PACAP expression might be under the strong influence of kisspeptin neurons.
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BibTeX
@article{tumurbaatar2026regulation,
title = {{Regulation of PACAP gene expression by ovarian sex steroids and kisspeptin: Study using hypothalamic cell lines and an in vivo female rat model}},
author = {Tuvshintugs Tumurbaatar and Aki Oride and Zhuoma Cairang and Hiroe Okada and Haruhiko Kanasaki},
journal = {Biochemistry and Biophysics Reports},
year = {2026},
month = oct,
doi = {10.1016/j.bbrep.2026.102834},
url = {https://doi.org/10.1016/j.bbrep.2026.102834},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Regulation of PACAP gene expression by ovarian sex steroids and kisspeptin: Study using hypothalamic cell lines and an in vivo female rat model
AU - Tuvshintugs Tumurbaatar
AU - Aki Oride
AU - Zhuoma Cairang
AU - Hiroe Okada
AU - Haruhiko Kanasaki
PY - 2026
DA - 2026/10/17
JO - Biochemistry and Biophysics Reports
DO - 10.1016/j.bbrep.2026.102834
UR - https://doi.org/10.1016/j.bbrep.2026.102834
AB - Objective: We investigated the effects of sex steroid hormones on hypothalamic PACAP expression. In addition, the mutual interaction of PACAP and kisspeptin was examined using hypothalamic cell models and an in vivo rat model. Materials and methods: The effects of estradiol (E2), progesterone (P4), and dihydrotestosterone (DHT) on PACAP gene expression was examined using the GT1-7, rHypoE-8, and mHypoA-55 cell lines. The effect of PACAP on Kiss-1 gene expression and the effect of kisspeptin on PACAP gene expression were also examined. In addition, PACAP and Kiss-1 gene expression in the hypothalamus was determined in ovariectomized (OVX) and ovary-intact rats with and without sex steroid hormone supplementation. Results: PACAP gene expression was not modulated by E2 or P4 stimulation, but DHT stimulation slightly increased its expression in GT1-7, rHypoE-8, and mHypoA-55. Stimulation with 100 nM PACAP significantly increased Kiss-1 gene expression in all three hypothalamic cell lines. Similarly, stimulation with 100 nM kisspeptin-10 also increased PACAP gene expression. PACAP gene expression within the posterior part of the hypothalamus was increased after OVX, and the OVX-induced increase in PACAP gene expression was suppressed by supplementation with E2, P4, and DHT, showing a pattern similar to that observed for Kiss-1 gene expression. In ovary-intact female rats, E2 administration, but not P4 or DHT, reduced PACAP gene expression. Conclusion: PACAP expression within the hypothalamus may not be regulated directly by E2 and P4. Although PACAP and kisspeptin mutually interact and regulate each other, PACAP expression might be under the strong influence of kisspeptin neurons.
SN - 2405-5808
ER -