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用于监测中枢性性早熟女童治疗的 kisspeptin 和 DLK1 水平。

Kisspeptin and DLK1 levels for monitoring treatment of girls with central precocious puberty.

作者信息

Onsoi Witchuwan, Numsriskulrat Nattakarn, Aroonparkmongkol Suphab, Supornsilchai Vichit, Srilanchakon Khomsak

机构信息

Division of Endocrinology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Division of Academic Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

出版信息

Clin Exp Pediatr. 2024 Jun;67(6):296-302. doi: 10.3345/cep.2023.01361. Epub 2024 May 21.

Abstract

BACKGROUND

Kisspeptin and delta-like 1 homolog (DLK1) are neuropeptides that reportedly play an important role in pubertal timing by activating and inhibiting the hypothalamic-pituitary-gonadal axis, respectively. Consequently, serum kisspeptin and DLK1 levels may be novel biomarkers for differentiating between central precocious puberty (CPP) and premature thelarche (PT) in girls and used to monitor CPP treatment.

PURPOSE

To compare baseline serum kisspeptin and DLK1 levels in girls with CPP at diagnosis and after treatment to age-matched girls with PT.

METHODS

This prospective longitudinal study included girls with precocious puberty and girls with PT who experienced breast development before 8 years of age and peak luteinizing hormone levels of ≥6 versus <6 IU/L after a gonadotropin-releasing hormone (GnRH) stimulation test. Serum kisspeptin and DLK1 levels were determined in both groups at baseline and after 6 months of GnRH analog treatment in the CPP group and analyzed by enzyme-linked immunosorbent assay.

RESULTS

The study divided a total of 48 girls into CPP (n=24; mean age, 7.7±0.7 years) and PT (n=24; mean age, 7.4±0.8 years) groups. The baseline median serum kisspeptin levels were 50.5 pg/mL (range, 38.2-77 pg/mL) and 49.5 pg/mL (range, 39.7-67.6 pg/mL), respectively (P=0.89), while the baseline median serum DLK1 levels were 6.5 ng/mL (range, 5.9-7.5 ng/mL) and 6 ng/mL (4.4-14.4 ng/mL), respectively (P=0.68). After 6 months of GnRH analog treatment in the CPP group, the median serum kisspeptin level was lower (46.4 ng/mL; range, 37.1-60 ng/mL) than that at baseline (P=0.002), while the median serum DLK1 level was higher (7 ng/mL; range, 6.7-8.9) than that at baseline (P=0.002).

CONCLUSION

Our findings suggest that baseline serum kisspeptin and DLK1 levels are not reliable biomarkers for differentiating between CPP and PT. However, significant changes in serum kisspeptin and DLK1 levels may be used to monitor CPP treatment.

摘要

背景

据报道,亲吻素和δ样1同源物(DLK1)是神经肽,分别通过激活和抑制下丘脑-垂体-性腺轴在青春期启动中发挥重要作用。因此,血清亲吻素和DLK1水平可能是区分女孩中枢性性早熟(CPP)和乳房过早发育(PT)的新型生物标志物,并可用于监测CPP的治疗。

目的

比较诊断时及治疗后CPP女孩与年龄匹配的PT女孩的血清亲吻素和DLK1基线水平。

方法

这项前瞻性纵向研究纳入了性早熟女孩和PT女孩,她们在8岁前出现乳房发育,促性腺激素释放激素(GnRH)刺激试验后促黄体生成素峰值水平≥6与<6 IU/L。在基线时以及CPP组GnRH类似物治疗6个月后,测定两组的血清亲吻素和DLK1水平,并通过酶联免疫吸附测定法进行分析。

结果

该研究共将48名女孩分为CPP组(n = 24;平均年龄,7.7±0.7岁)和PT组(n = 24;平均年龄,7.4±0.8岁)。基线时血清亲吻素水平中位数分别为50.5 pg/mL(范围,38.2 - 77 pg/mL)和49.5 pg/mL(范围,39.7 - 67.6 pg/mL)(P = 0.89),而基线时血清DLK1水平中位数分别为6.5 ng/mL(范围,5.9 - 7.5 ng/mL)和6 ng/mL(4.4 - 14.4 ng/mL)(P = 0.68)。CPP组GnRH类似物治疗6个月后,血清亲吻素水平中位数(46.4 ng/mL;范围,37.1 - 60 ng/mL)低于基线水平(P = 0.002),而血清DLK1水平中位数(7 ng/mL;范围,6.7 - 8.9)高于基线水平(P = 作0.002)。

结论

我们的研究结果表明,基线血清亲吻素和DLK1水平不是区分CPP和PT的可靠生物标志物。然而,血清亲吻素和DLK1水平的显著变化可用于监测CPP的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc81/11150982/9744563161ae/cep-2023-01361f1.jpg

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