Crosstalk between kisspeptin and gonadotropin-inhibitory hormone in the silence of puberty: preclinical evidence from a calcium signaling study.
Bulut. Ferah F; Kacar. Emine E; Bilgin. Batuhan B; Hekim. Munevver Gizem MG; Keleştemur. Muhammed Mirac MM; Sahin. Zafer Z; Ayar. Ahmet A; Ozcan. Mete M
Key Findings
- Kisspeptin‑10 (100‑1000 nM) sharply increases intracellular calcium in hypothalamic rHypoE‑8 cells.
- A kisspeptin receptor antagonist (P234) blocks the calcium response, confirming receptor‑mediated action.
- GnIH alone does not alter basal calcium but significantly attenuates the kisspeptin‑induced calcium rise.
Practical Outcomes
- The study shows how kisspeptin can directly activate hypothalamic neurons at the cellular level, but it provides no human dosing, safety, or performance data. For biohackers, it suggests that any kisspeptin supplementation would need to consider receptor activation and possible interaction with GnIH, yet no concrete protocol can be derived from this in‑vitro work.
Summary
In a lab study using mouse hypothalamus cells, the short form of kisspeptin (kisspeptin‑10) caused a strong rise in internal calcium levels, which is a signal that neurons are active. This effect could be blocked by a kisspeptin receptor blocker, and another hormone, GnIH, didn’t change calcium on its own but reduced the kisspeptin‑driven calcium spikes. The work suggests kisspein‑10 directly stimulates its own neurons and that GnIH can dampen this signal.
Abstract
Kisspeptin and gonadotropin-inhibitory hormone (GnIH) are among suggested neuroendocrine modulators of reproductive function. Intracellular calcium signaling is a critical component in the regulation of a variety of physiological and pathological processes including neurotransmitter release, and, therefore, can be used as signaling indicator for investigating the involvement of kisspeptin, GnIH, and gonadotropin-releasing hormone (GnRH) release. Hence, this study investigated the effects of kisspeptin and GnIH on calcium signaling using immortalized hypothalamic cells (rHypoE-8) as a model. Kisspeptin neurons were loaded with the ratiometric calcium dye (Fura-2 AM, 1 μmol) and intracellular free calcium ([Ca<sup>2+</sup>]<sub>i</sub>) responses were quantified using digital fluorescence imaging system. Kisspeptin-10 (100, 300, and 1000 nM) caused a significant increase in [Ca<sup>2+</sup>]<sub>i</sub> in rHypoE-8 cells (<i>n</i> = 58, <i>n</i> = 64, and <i>n</i> = 49, respectively, <i>p</i> < 0.001). The kisspeptin receptor antagonist, P234, inhibited the calcium responses to kisspeptin (<i>p</i> < 0.001, <i>n</i> = 32). GnIH (100 and 1000 nM), alone, did not cause any significant change in the mean basal [Ca<sup>2+</sup>]<sub>i</sub> levels in kisspeptin cells, but GnIH attenuated the kisspeptin-evoked [Ca<sup>2+</sup>]<sub>i</sub> transients (<i>n</i> = 47, <i>p</i> < 0.001). This novel findings of [Ca<sup>2+</sup>]<sub>i</sub> signaling in <i>in vitro</i> setting implicate that kisspeptin and GnIH may exert their effects on hypothalamus-pituitary-gonadal (HPG) axis by modulating kisspeptin neurons. These results also implicate that kisspeptin neurons may have an autocrine regulation.
Study Information
pubmed
2022
2022-09-22T00:00:00.000Z
10.1080/10799893.2022.2125014
2
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