Expression of functional KISS1 and KISS1R system is altered in human pituitary adenomas: evidence for apoptotic action of kisspeptin-10.
Martínez-Fuentes. Antonio J AJ; Molina. Marcelo M; Vázquez-Martínez. Rafael R; Gahete. Manuel D MD; Jiménez-Reina. Luis L; Moreno-Fernández. Jesús J; Benito-López. Pedro P; Quintero. Ana A; de la Riva. Andrés A; Diéguez. Carlos C; Soto. Alfonso A; Leal-Cerro. Alfonso A; Resmini. Eugenia E; Webb. Susan M SM; Zatelli. Maria C MC; degli Uberti. Ettore C EC; Malagón. María M MM; Luque. Raul M RM; Castaño. Justo P JP
Key Findings
- Normal pituitary tissue expresses both KISS1 and its receptor KISS1R, but many pituitary tumors lose this expression pattern.
- Kisspeptin‑10 causes a strong rise in intracellular calcium in most growth‑hormone‑producing tumor cells, but not in non‑functioning tumor cells.
- Kisspeptin‑10 increases the rate of apoptosis (programmed cell death) in both types of pituitary tumor cells studied.
Practical Outcomes
- For biohackers, this research mainly highlights a potential anti‑cancer property of kisspeptin‑10, but it offers no dosage guidance, safety data, or proven benefits for healthy individuals. At present it isn’t a usable protocol for longevity or performance enhancement.
Summary
The study found that the hormone‑like peptide kisspeptin‑10 can trigger cell‑death signals in pituitary tumor cells, especially those that make growth hormone, but it doesn’t show any clear benefit or safe way to use it for healthy people looking to improve longevity or performance.
Abstract
KISS1 was originally identified as a metastasis-suppressor gene able to inhibit tumor progression. KISS1 gene products, the kisspeptins, bind to a G-protein-coupled receptor (KISS1R, formerly GPR54), which is highly expressed in placenta, pituitary, and pancreas, whereas KISS1 mRNA is mainly expressed in placenta, hypothalamus, striatum, and pituitary. KISS1/KISS1R pituitary expression profile, coupled to their anti-tumoral capacities, led us to hypothesize that this system may be involved in the biology of pituitary tumors. To explore this notion, expression levels of KISS1R and KISS1 were evaluated in normal and adenomatous pituitaries. Additionally, functionality of this system was assessed by treating dispersed pituitary adenoma cells in primary culture with kisspeptin-10 and evaluating intracellular calcium kinetics and apoptotic rate. Both KISS1 and KISS1R were expressed in normal pituitary, whereas this simultaneous expression was frequently lost in pituitary tumors, where diverse patterns of KISS1/KISS1R expression were observed that differed among distinct types of pituitary adenomas. Measurement of calcium kinetics revealed that kisspeptin-10 elicits a remarkable increase in [Ca(2+)](i) in individual cells from four out of the five GH-producing adenomas studied, whereas cells derived from non-functioning pituitary adenomas (NFPA, n=45) did not respond. In contrast, kisspeptin-10 treatment increased the apoptotic rate in cells derived from both GH-producing and NFPA. These results provide primary evidence that KISS1 and KISS1R expression can be differentially lost in pituitary tumor subtypes, where this system can exert functional, proapoptotic actions, and thereby offer novel insights to investigate the biology and therapeutic options to treat these tumors.
Study Information
pubmed
2010
2010-12-17T00:00:00.000Z
10.1530/eje-10-0905