From 2b402d141c9543bcd9883b21eb87fca7fdd18de3 Mon Sep 17 00:00:00 2001 From: johnnie0863959 Date: Thu, 2 Apr 2026 16:07:30 +0800 Subject: [PATCH] Add m6A mRNA methylation regulates testosterone synthesis through modulating autophagy in Leydig cells --- ...nthesis-through-modulating-autophagy-in-Leydig-cells.md | 7 +++++++ 1 file changed, 7 insertions(+) create mode 100644 m6A-mRNA-methylation-regulates-testosterone-synthesis-through-modulating-autophagy-in-Leydig-cells.md diff --git a/m6A-mRNA-methylation-regulates-testosterone-synthesis-through-modulating-autophagy-in-Leydig-cells.md b/m6A-mRNA-methylation-regulates-testosterone-synthesis-through-modulating-autophagy-in-Leydig-cells.md new file mode 100644 index 0000000..c2fbd54 --- /dev/null +++ b/m6A-mRNA-methylation-regulates-testosterone-synthesis-through-modulating-autophagy-in-Leydig-cells.md @@ -0,0 +1,7 @@ +
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In this study, the treatment using MTOR inhibitor rapamycin failed to alter the levels of LC3B-II, SQSTM1, p-PRKAA2 Thr172, p-ULK1 Ser555, and p-ULK1 Ser757 in HsCG-treated TM3 cells and primary LCs (Figure 3Aand S3A). Macroautophagy/autophagy is indispensable for testosterone synthesis in Leydig cells (LCs), and here we report a negative association between m6A modification and autophagy in LCs during testosterone synthesis. SIRT1 mediates the degradation of NHERF2 through autophagy, thereby weakening its negative regulatory effect on the high-density lipoprotein receptor SRB1 in Leydig cells. Finally, stress (hypoxia)-induced autophagy does not change the ABP expression in primary Sertoli cells, which supports the idea that the autophagic degradation of ABP may be a selectively regulated process. To verify these results, we further treated the cells with testosterone, which inhibited the autophagic degradation of ABP (Fig. 3F). To detect whether testosterone regulates autophagy in Sertoli cells, we treated the cells with CM, medium with charcoal stripped serum (MCSS) and MCSS with testosterone. The results showed that testosterone considerably increased the ABP mRNA and protein levels in primary cells and testosterone promoted the secretion of ABP to the supernatant. +We then assessed the expression of NHERF2 and SR-BI by immunofluorescence. (A) The knockdown of Nherf2 by shRNA could reduce NHERF2 expression effectively. (N) The LIR motif of NHERF2 is essential for its degradation. +A complicated study demonstrated that [buy testosterone supplements](http://downarchive.org/user/denimllama0/) acts as a specific switch controller to selectively manipulate the autophagic degradation of ABP in rat SCs . Another crucial function of SCs is to secrete androgen-binding protein (ABP), a testicular glycoprotein facilitating the transportation of testosterone and dihydrotestosterone . In addition to LCs, Sertoli cells (SCs) are another vital somatic cell comprising seminiferous tubules found in testis, providing nutrition and [https://noticias-sociales.space](https://noticias-sociales.space/item/595450) protection for the developing spermatozoa. +Our data revealed that HsCG treatment significantly reduced m6A levels at two sites within 3ʹUTR of the Ppm1a transcript, but displayed no impact on other m6A modification sites within CDS. Accumulating evidence has confirmed that reduced expression of METTL3 or loss-of-function mutation in METTL14 may result in lowered m6A levels . Together, these results highlight a vital role of m6A mRNA methylation in regulating testosterone synthesis through modulating autophagy in LCs. Following HsCG treatment, reduced m6A slowed down the regulation of m6A on these transcripts, leading to increased CAMKK2 levels but reduced PPM1A levels. In the testis, LHCGR is detected in both Sertoli cells and LCs, with the latter being the source of testosterone 3,51. Growing evidence has supported that autophagy is vital for testosterone synthesis in LCs 3,4. +Table S1 shows characteristics of human patients in the normal serum testosterone level. Subsequently, NHERF2 levels were measured using immunoblotting. The 2ΔΔCt method was used to calculate the fold changes in gene expression. The RNA was pretreated with DNase (RNase-free DNase set; QIAGEN) according to the manufacturer’s instructions. Total RNA was extracted from the control and treatment groups using the RNeasy Mini kit (74104; QIAGEN) according [best place to buy testosterone](https://lovewiki.faith/wiki/Compounded_Testosterone_Cream) the manufacturer’s instructions. The homogenates were centrifuged at 12,000 rpm for 15 min, and the protein concentrations were determined using a protein assay from Bio-Rad Laboratories. +
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