Mechanism of melatonin regulation of PI3K/Akt/mTOR signaling in hypothalamus delaying the initiation of puberty in female mice mice

CHEN Zi-Xuan; SI Li-Na; SHU Wei-Han; ZHANG Xin; WEI Chen-Yang; CHENG Lu-Yang; YANG Song-He; QIAO Yue-Bing

doi:10.16098/j.issn.0529-1356.2023.06.004

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Acta Anatomica Sinica ›› 2023, Vol. 54 ›› Issue (6) : 644-651. DOI: 10.16098/j.issn.0529-1356.2023.06.004

Mechanism of melatonin regulation of PI3K/Akt/mTOR signaling in hypothalamus delaying the initiation of puberty in female mice mice

CHEN Zi-xuan¹ SI Li-na¹ SHU Wei-han² ZHANG Xin¹ WEI Chen-yang¹ CHENG Lu-yang² YANG Song-he^1*QIAO Yue-bing^1*

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Abstract

Objective To explore the effect of melatonin (MLT) on the initiation of puberty in female mice and on the expression level of phosphatidylinositol-3-kinases (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in the hypothalamus. Methods Seventy-eight 20-day-old female KM mice were randomly divided into melatonin (MLT) group and normal saline (NS) group, with 39 mice in each group. Starting at 22 days of age, the MLT group was given a subcutaneous injection of 1mg/kg melatonin and the NS group was given an equal volume of saline. Thirty-two days of age were selected as the sampling point before puberty initiation and 13 mice were executed in each of the two groups, while 37 and 42 days of age were selected as the sampling point after puberty initiation and 13 mice were executed in each of the two groups. Observation of vaginal opening time in mice, weighing of ovaries and uterus to calculate organ indices. HE staining to observe the number of ovarian corpora lutea. The levels of serum luteinizing hormone（LH）were determined by ELISA. The mRNA and protein expression levels of PI3K/Akt/mTOR pathway in hypothalamus were detected by Real-time PCR and Western blotting. Results Compared with the normal saline group, mice in the melatonin group had significantly delayed vaginal opening time (P<0.05), decreased significantly ovarian and uterine volume and index (P<0.05), decreased significantly serum LH levels (P<0.05), and decreased significantly mRNA and protein expression levels of the hypothalamic PI3K/Akt/mTOR pathway(P<0.05). Conclusion Melatonin delays puberty initiation in mice by a mechanism that may be related to inhibition of the hypothalamic PI3K/Akt/mTOR signalling pathway.

Key words

Melatonin

/ Puberty onset / Hypothalamic-pituitary-gonad axis / Phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway / Enzyme-linked immunosorbent assay / Mouse

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CHEN Zi-xuan SI Li-na SHU Wei-han ZHANG Xin WEI Chen-yang CHENG Lu-yang YANG Song-he QIAO Yue-bing.

Mechanism of melatonin regulation of PI3K/Akt/mTOR signaling in hypothalamus delaying the initiation of puberty in female mice mice

[J]. Acta Anatomica Sinica. 2023, 54(6): 644-651 https://doi.org/10.16098/j.issn.0529-1356.2023.06.004

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