Zhou Lili, Ren Yaoquan, Li Dongmei, Zhou Weiwei, Li Chengke, Wang Qiang, Yang Xiangzheng
Pediatrics Department, Beijing University of Chinese Medicine Shenzhen Hospital at Longgang, Shenzhen, China.
Pediatrics Department, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, China.
Acta Biochim Pol. 2023 Mar 16;70(1):183-190. doi: 10.18388/abp.2020_6450.
Precocious puberty (PP) has increasingly become a social concern. This study aimed to investigate the effect of timosaponin AIII (TAIII) on the precocious puberty and its possible mechanisms in mice. Four groups of mice consisting of controls that received saline or TAIII, a model that received leptin to induce precocious puberty (PP), and leptin+TAIII (the leptin model treated with TAIII) were used to determine the effect of TAIII on PP. Pathological and cytological examinations were conducted to investigate the signs and onset of PP and the development of reproductive organs. The level of serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E2) were determined using enzyme-linked immunosorbent assay (ELISA). The expression of genes related to the hypothalamic-pituitary-gonadal axis (HPGA) was assessed using qRT-PCR and Western blotting. Bone mineral density (BMD) was determined using high resolution peripheral quantitative computed tomography. In mice treated with leptin, earlier vaginal opening and estrus were observed, as well as the increased ovarian and uterine weight, total uterine cross-sectional size, number of corpora lutea, and elevated serum sex hormone levels and HPGA expression. On the other hand, TAIII treatment delayed the vaginal opening and vaginal estrus to 32.1 and 37.5 days after birth, and delayed the development of reproductive organs, leading to significantly smaller uterus and ovary size, less corpora lutea and low BMD (P<0.05). In addition, the serum levels of LH, FSH and E2 were significantly reduced (P<0.05) and so was the expression of HPGA and leptin genes (P<0.05). Our experimental data demonstrated that TAIII has activity against leptin-induced PP activity and may attenuate PP by reducing reproductive hormones and deactivating the hypothalamic-pituitary-gonadal axis through downregulating leptin expression.
性早熟（PP）日益成为一个社会关注的问题。本研究旨在探讨知母皂苷AIII（TAIII）对小鼠性早熟的影响及其可能的作用机制。将四组小鼠用于确定TAIII对性早熟的影响，包括接受生理盐水或TAIII的对照组、接受瘦素诱导性早熟（PP）的模型组以及瘦素+TAIII组（用TAIII处理的瘦素模型组）。进行病理和细胞学检查以研究性早熟的体征和发病情况以及生殖器官的发育。使用酶联免疫吸附测定（ELISA）法测定血清促黄体生成素（LH）、促卵泡生成素（FSH）和雌二醇（E2）的水平。使用qRT-PCR和蛋白质免疫印迹法评估下丘脑-垂体-性腺轴（HPGA）相关基因的表达。使用高分辨率外周定量计算机断层扫描测定骨密度（BMD）。在用瘦素处理的小鼠中，观察到阴道开口和发情提前，以及卵巢和子宫重量增加、子宫总横截面积增大、黄体数量增多，血清性激素水平和HPGA表达升高。另一方面，TAIII处理将阴道开口和阴道发情推迟至出生后32.1天和37.5天，并延缓了生殖器官的发育，导致子宫和卵巢尺寸显著变小、黄体减少且骨密度降低（P<0.05）。此外，血清LH、FSH和E2水平显著降低（P<0.05），HPGA和瘦素基因的表达也显著降低（P<0.05）。我们的实验数据表明，TAIII具有对抗瘦素诱导的性早熟活性，可能通过降低生殖激素并下调瘦素表达使下丘脑-垂体-性腺轴失活来减轻性早熟。
