Department of Cell Biology, Physiology and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), and CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), University of Córdoba, Córdoba, Spain.
Eur J Endocrinol. 2011 Mar;164(3):355-62. doi: 10.1530/EJE-10-0905. Epub 2010 Dec 17.
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+) 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.
KISS1 最初被鉴定为一种具有抑制肿瘤进展能力的转移抑制基因。KISS1 基因产物，即 kisspeptins，与 G 蛋白偶联受体（KISS1R，以前称为 GPR54）结合，该受体在胎盘、垂体和胰腺中高度表达，而 KISS1 mRNA 主要在胎盘、下丘脑、纹状体和垂体中表达。
KISS1/KISS1R 垂体表达谱及其抗肿瘤能力使我们假设该系统可能参与垂体肿瘤的生物学。为了探索这一概念，评估了正常和腺瘤性垂体中 KISS1R 和 KISS1 的表达水平。此外，通过用 kisspeptin-10 处理原代培养的分散垂体腺瘤细胞，并评估细胞内钙动力学和凋亡率，评估了该系统的功能。
正常垂体中均表达 KISS1 和 KISS1R，而这种同时表达在垂体肿瘤中经常丢失，在不同类型的垂体腺瘤中观察到不同的 KISS1/KISS1R 表达模式。钙动力学测量表明，kisspeptin-10 在研究的 5 个 GH 分泌性腺瘤中的 4 个个体细胞中引起显著的Ca(2+)增加，而来自无功能垂体腺瘤（NFPA，n=45）的细胞没有反应。相比之下，kisspeptin-10 处理增加了来自 GH 分泌性腺瘤和 NFPA 的细胞的凋亡率。
这些结果提供了初步证据，表明 KISS1 和 KISS1R 的表达可以在垂体肿瘤亚型中不同程度地丢失，该系统可以发挥功能促凋亡作用，从而为研究这些肿瘤的生物学和治疗选择提供新的见解。
