Kisspeptin induces Kiss-1 and GnRH gene expression in mHypoA-55 hypothalamic cell models: Involvement of the ERK and PKA signaling pathways.
Tumurbaatar. Tuvshintugs T; Kanasaki. Haruhiko H; Yacca. Susdiaman Sudin SS; Cairang. Zhuoma Z; Tumurgan. Zolzaya Z; Oride. Aki A; Okada. Hiroe H; Kyo. Satoru S
Key Findings
- Kisspeptin‑10 increases Kiss‑1 and GnRH gene expression in hypothalamic cells.
- The increase is linked to activation of ERK (via MEK) and PKA signaling pathways.
- Blocking either the MEK/ERK pathway (with PD098059) or the PKA pathway (with H89) reduces the kisspeptin‑10‑driven gene expression.
Practical Outcomes
- For biohackers, this research suggests that kisspeptin can influence the hormonal axis that controls reproduction, but it’s limited to cell‑culture data with no human dosing information. It highlights that any future attempts to modulate kisspeptin signaling should consider both ERK and PKA pathways, yet there’s no ready‑to‑use protocol or safety guidance from this study.
Summary
The study shows that a short form of the hormone kisspeptin (kisspeptin‑10) can boost the production of its own gene (Kiss‑1) and the hormone GnRH in mouse hypothalamic cells, and that this effect relies on two cell‑signaling pathways called ERK and PKA.
Abstract
mHypoA-55 cells are kisspeptin-expressing neuronal cells originating from the arcuate nucleus of the mouse hypothalamus. These cells are called KNDy neurons because they co-express kisspeptin, neurokinin B, and dynorphin A. In addition, they express gonadotropin-releasing hormone (GnRH). Here, we found that kisspeptin 10 (KP10) increased Kiss-1 (encoding kisspeptin) and GnRH gene expression in kisspeptin receptor (Kiss-1R)-overexpressing mHypoA-55 cells. KP10 greatly increased serum response element (SRE) promoter activity, which is a target of extracellular signal-regulated kinase (ERK) (20.0 ± 2.54-fold). KP10 also increased cAMP-response element (CRE) promoter activity in these cells (2.32 ± 0.36-fold). KP10-increased SRE promoter activity was significantly prevented in the presence of PD098095, a MEK kinase (MEKK) inhibitor, and KP10-induced CRE promoter activity was also inhibited by PD098059. Similarly, H89, a protein kinase A (PKA) inhibitor, significantly inhibited the KP10 induction of SRE and CRE promoters. KP10-induced Kiss-1 and GnRH gene expressions were inhibited in the presence of PD098059. Likewise, H89 significantly inhibited the KP10-induced increase in Kiss-1 and GnRH. Transfection of mHypoA-55 cells with constitutively active MEKK (pFC-MEKK) increased SRE and CRE promoter activities by 9.75 ± 1.77- and 1.36 ± 0.12-fold, respectively. Induction of constitutively active PKA (pFC-PKA) also increased SRE and CRE promoter activities by 2.41 ± 0.42- and 40.71 ± 7.77-fold, respectively. Furthermore, pFC-MEKK and -PKA transfection of mHypoA-55 cells increased both Kiss-1 and GnRH gene expression. Our current observations suggest that KP10 increases both the ERK and PKA pathways and that both pathways mutually interact in mHypoA-55 hypothalamic cells. Activation of both ERK and PKA signaling might be necessary to induce Kiss-1 and GnRH gene expressions.
Study Information
pubmed
2023
2023-03-16T00:00:00.000Z
10.1016/j.ygcen.2023.114260
2
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