Arg-Phe-amide-related peptides influence gonadotropin-releasing hormone neurons.
Kelestimur. Haluk H; Kacar. Emine E; Uzun. Aysegul A; Ozcan. Mete M; Kutlu. Selim S
Key Findings
- Kisspeptin‑10 (100 nM) significantly increases GnRH release and intracellular calcium in GT1‑7 cells.
- Co‑treatment with 1 µM gonadotropin‑inhibitory hormone or Arg‑Phe‑amide‑related peptide‑1 reduces kisspeptin‑induced GnRH release.
- The reduction in GnRH release occurs without affecting the kisspeptin‑induced calcium increase, suggesting a calcium‑independent inhibitory pathway.
Practical Outcomes
- For biohackers, the data hint that kisspeptin could be used to stimulate the reproductive hormone axis, but other naturally occurring peptides might blunt that effect. However, the work is purely in vitro, so no dosing or safety guidance can be drawn for humans yet. More animal and clinical research is needed before any real‑world protocol can be recommended.
Summary
In a lab study using mouse hypothalamic cells, the peptide kisspeptin‑10 boosted the release of the hormone GnRH and raised calcium inside the cells. When the cells were also given either gonadotropin‑inhibitory hormone or a related Arg‑Phe‑amide peptide, the extra GnRH caused by kisspeptin was cut down, but the calcium rise stayed the same. This means those other peptides can dampen kisspeptin’s effect on hormone release without touching calcium signals.
Abstract
The hypothalamic Arg-Phe-amide-related peptides, gonadotropin-inhibitory hormone and orthologous mammalian peptides of Arg-Phe-amide, may be important regulators of the hypothalamus-pituitary-gonadal reproductive axis. These peptides may modulate the effects of kisspeptins because they are presently recognized as the most potent activators of the hypothalamus-pituitary-gonadal axis. However, their effects on gonadotropin-releasing hormone neurons have not been investigated. In the current study, the GT1-7 cell line-expressing gonadotropin-releasing hormone was used as a model to explore the effects of Arg-Pheamide-related peptides on kisspeptin activation. Intracellular calcium concentration was quantified using the calcium-sensitive dye, fura-2 acetoxymethyl ester. Gonadotropin-releasing hormone released into the medium was detected via enzyme-linked immunosorbent assay. Results showed that 100 nmol/L kisspeptin-10 significantly increased gonadotropin-releasing hormone levels (at 120 minutes of exposure) and intracellular calcium concentrations. Co-treatment of kisspeptin with 1 μmol/L gonadotropin-inhibitory hormone or 1 μmol/L Arg-Phe-amide-related peptide-1 significantly attenuated levels of kisspeptin-induced gonadotropin-releasing hormone but did not affect kisspeptin-induced elevations of intracellular calcium concentration. Overall, the results suggest that gonadotropin-inhibitory hormone and Arg-Phe-amide-related peptide-1 may have inhibitory effects on kisspeptin-activated gonadotropin-releasing hormone neurons independent of the calcium signaling pathway.
Study Information
pubmed
2013
2013-06-25T00:00:00.000Z
10.3969/j.issn.1673-5374.2013.18.009
3
51