肌醇-三磷酸3-激酶B通过抑制线粒体自噬导致衰老睾丸间质细胞睾酮合成障碍

doi:10.3969/j.issn.1006-5725.2024.24.001

Abstract

Abstract:

Objective To explore the effect and mechanism of ITPKB on testosterone synthesis disorder of senescent Leydig cells. Methods A comprehensive analysis of public datasets was performed using GO， GSEA enrichment analysis and protein interaction network to determine the expression of related pathways and genes in testicular tissue in aging-related diseases. D-galactose intraperitoneal injection to construct an aging mouse model； Mouse Leydig cells （TM3） were cultured， and the cells were divided into four groups， control group （NC group）， senescence group （D-gal group）， inhibitor group （GNF362 group） and D-gal+GNF362 group. The serum levels of testosterone， follicle-stimulating hormone and luteinizing hormone in mice were detected by ELISA. q-PCR was used to detect the mRNA levels of IL-1α， IL-6， TNF-α and ITPKB. Immunofluorescence was used to detect the protein expressions of StAR， 3β-HSD， ITPKB and LC3. Western blot was used to detect the protein expressions of P53， P21， StAR and ITPKB. Transmission electron microscopy to observe intracellular structures. Results Bioinformatics analysis showed that ITPKB was highly expressed in the testes of aging mice. The serum testosterone level of aging mice was lower than that of young mice. Compared with the younger group， the mRNA levels of IL-1α， IL-6， TNF-α and ITPKB in the testes of mice in the aging group were increased， and the protein levels of P53， P21 and ITPKB were increased. The levels of StAR， 3β-HSD， LC3 protein and mitophagy decreased. Compared with the cells in the D-gal group， the testosterone level in the supernatant of the D-gal+GNF362 group was increased， and the level of mitophagy was significantly increased. Conclusion ITPKB causes impaired testosterone synthesis in senescent Leydig cells by inhibiting mitophagy.

Key words: late-onset hypogonadism, testosterone deficiency, inositol-trisphosphate 3-kinase B, aging, testosterone replacement therapy, mitophagy

CLC Number:

R698

Ziguang LI,Cun WEI,Lei ZHAO,Qizhao. ZHOU. Inositol⁃trisphosphate 3⁃kinase B causes impaired testosterone synthesis in senescent leydig cells by inhibiting mitophagy[J]. The Journal of Practical Medicine, 2024, 40(24): 3427-3437.

Figures/Tables 9

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引物名称	引物序列（前引物）	引物序列（后引物）
Gapdh	GGACCTGACCTGCCGTCTAG	GTAGCCCAGGATGCCCTTGA
Itpkb	GGCTGAATAGTAGCAGCGGTA	CTGGTTCACCTGCACATTTTG
Il?1α	AGTATCAGCAACGTCAAGCAA	TCCAGATCATGGGTTATGGACTG
Il?6	CTGCAAGAGACTTCCATCCAG	AGTGGTATAGACAGGTCTGTTGG
Tnf?α	CCTGTAGCCCACGTCGTAG	GGGAGTAGACAAGGTACAACCC

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Inositol⁃trisphosphate 3⁃kinase B causes impaired testosterone synthesis in senescent leydig cells by inhibiting mitophagy

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