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| Improvement effect of obacunone on true precocious puberty in female rats by regulating the Notch1/Hes1 pathway |
| Hits 20 Download times 3 Received:October 16, 2024 |
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| DOI
10.11656/j.issn.1672-1519.2025.04.12 |
| Key Words
obacunone;Notch1/Hes1 pathway;true precocious puberty;hypothalamic-pituitary-gonadal axis |
| Author Name | Affiliation | E-mail | | HU Yingjie | Department of Traditional Chinese Medicine, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450053, China | | | LI Jing | Department of Traditional Chinese Medicine, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450053, China | | | ZHANG Suling | Department of Traditional Chinese Medicine, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450053, China | | | YUE Shangsai | Department of Traditional Chinese Medicine, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450053, China | | | FU Yunyun | Department of Traditional Chinese Medicine, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450053, China | | | SUN Fengping | Department of Traditional Chinese Medicine, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450053, China | sunfengping1981@126.com |
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| Abstract
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| [Objective] To investigate the modulation of the Notch1/Hes1 pathway by obacunone（Oba） on the improvement of true precocious puberty（TPP） in female rats. [Methods] Female rats were randomly assigned to seven groups：the TPP group，normal group，Oba low-dose group，Oba high-dose group，leuprolide group，and Oba high-dose+Notch1 blocker（DAPT） group，with 12 rats in each group. Except for the normal group，the TPP model was established in the remaining groups by subcutaneous injection of N-methyl-DL-aspartic acid. After successful model induction，drug treatment was initiated and administered once daily for 2 weeks. The time of vaginal opening was recorded. Enzyme-linked immunosorbent assay（ELISA） was used to measure the serum levels of luteinizing hormone（LH），estradiol（E2），and follicle-stimulating hormone（FSH）. Changes in ovarian and uterine coefficients were assessed. Hematoxylin and eosin（HE） staining was performed to examine pathological changes in the ovaries and uterus. Immunohistochemical staining was used to detect the expression of gonadotropin-releasing hormone（GnRH） in the hypothalamus and gonadotropin-releasing hormone receptor（GnRHR） in the pituitary gland. Additionally，the protein expression of Notch1 and Hes1 was evaluated by Western blot analysis. [Results] Compared with the normal group，rats in the TPP group showed multiple secondary follicles and tertiary follicles in the ovaries，thickening of the uterine wall，advancement of the vaginal opening time（P<0.05），elevation of serum levels of LH，E2，FSH，ovarian coefficients，uterine coefficients，the average optical density value of GnRH expression in the hypothalamus，and GnRHR expression in the pituitary gland（P<0.05），and elevation of hypothalamic expression of Notch1 and Hes1 protein. Notch1 and Hes1 protein expression in the hypothalamus decreased（P<0.05）；compared with the TPP group，the number of secondary and tertiary follicles in the ovaries of rats in the Oba low-dose group，Oba high-dose group，and leuprolide group decreased，the uterine wall thinned，and the time of vaginal opening was delayed（P<0.05），and the levels of LH，E2，and FSH in the serum，the coefficients of the ovary，the coefficients of the uterus，the coefficients of GnRH expression in the hypothalamus GnRH expression，the mean optical density value of GnRHR expression in the pituitary gland decreased（P<0.05），and the expression of Notch1 and Hes1 proteins in the hypothalamus was elevated（P<0.05）；compared with the Oba high-dose group，the number of secondary follicles and tertiary follicles increased in the ovaries of the rats in the Oba high-dose + DAPT group，the uterine wall thickened，and the time of vaginal opening was advanced（P<0.05），increased serum levels of LH，E2，FSH，ovarian coefficient，uterine coefficient，mean optical density value of GnRH expression in the hypothalamus，and mean optical density value of GnRHR expression in the pituitary gland（P<0.05），and decreased protein expression of Notch1 and Hes1 in the hypothalamus（P<0.05）. [Conclusion] Oba may improve TPP in female rats by up-regulating the Notch1/Hes1 pathway. |
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