Add 'Functional role of autophagy in testicular and ovarian steroidogenesis'

Functional-role-of-autophagy-in-testicular-and-ovarian-steroidogenesis.md

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+<br>Estrogen hormone perhaps deserves more attention because estrogen hormone plays a critical role not only in reproduction but is also implicated in the pathogenesis of breast cancer together with progesterone hormone signaling and auto-immune diseases such as systemic lupus erythematosus . Defective progesterone production may cause a wide range of reproductive problems, from defective implantation-related infertility to pregnancy-related complications such as miscarriage and preterm birth . Sex steroid hormones control diverse physiological processes, from sexual differentiation, somatic growth, metabolic function, reproduction, and immunity to gender-specific differences in brain function and behavior . This is also true for the actions of gonadotropin hormones on autophagy. First, long-term and in-vivo effects of autophagy inhibition cannot be predicted or extrapolated from our findings because they were obtained using ex vivo and in vitro culture conditions. Taken together, these findings may,  [graph.org](https://graph.org/Testosterone-Patches-03-31) at least in part, provide molecular evidence for compromised P4 production in these patients.
+The mammalian target of rapamycin (mTOR), a serine/threonine kinase, is a major regulator of cell growth, survival, metabolism, and immunity. Moreover, this review cannot fail to mention that endogenous estrogen signaling is essential for male reproduction . ABP is concentrated in the apical part of the SCs , promotes germ cell differentiation, and regulates spermatogenesis spatially . T, [buy testosterone injections](https://pads.jeito.nl/s/tsajPRryxL); ES, estradiol; NE, norepinephrine; NPY, neuropeptide; GABA, gamma-aminobutyric acid; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone; FSH, follicle-stimulating hormone; KISS, kisspeptin; AVPV, anteroventral periventricular nucleus. Testosterone is mainly synthesized in LCs, where autophagy has been reported to be extremely active 54,97.
+Herein, we presented a comprehensive overview on the effects of the regulation of autophagy on male reproduction, including its relation to spermatogenesis, the endocrinology of testis, and the key molecule of autophagy mechanism—the regulation of mTORC1 (Figure 4). Autophagy can maintain the survival of testicular cells or accelerate the apoptosis of some cells, representing a double-edged sword . As a central modulator in stem cell homeostasis, mTORC1 signaling governs stem cells quiescence 127,128. Retinoic acid (RA) is required for the self-renewal of spermatogonial stem cells (SSCs) and for subsequent entry into meiosis . In other words, high mTORC1 activity promotes biomolecular synthesis and simultaneously inhibits autophagy 124,125.
+In addition, NHERF2 protein levels increased in autophagy-deficient Leydig cells compared with control cells (Fig. 6 I). After treatment with the autophagy inhibitor, NHERF2 protein, but not the other two proteins, accumulated in the cells (Fig. 6 B). These results suggest that the decreased cholesterol pool in autophagy-deficient Leydig cells results from impaired cholesterol uptake likely induced by the down-regulation of the lipoprotein receptor SR-BI. Thus, the disruption of autophagy might not inhibit cholesterol synthesis in Leydig cells. Next, we determined the factors contributing to the decreased LD and cholesterol levels in autophagy-deficient Leydig cells. (C and D) Lipid and cholesterol storage were extremely reduced in autophagy-deficient Leydig cells. Dramatically reduced LDs and cholesterol in autophagy-deficient Leydig cells.
+CHX chase assay of NHERF2 in Atg7Flox/Flox and SF1-Atg7−/− (E) as well as Atg5Flox/Flox and SF1-Atg5−/− (G) Leydig cells. CHX chase assay of NHERF2 in HEK293T cells in the absence or presence of 3-MA. (C) NHERF2 was stabilized in autophagic flux–disrupted cells.
+And very recently, another group of investigators demonstrated in the porcine ovary that FSH promotes progesterone production by enhancing autophagy through the upregulation of Beclin1 via the PI3K/JNK/c-Jun pathway to accelerate LD degradation in porcine GCs . In the absence of Sirt1, LC3 fails to deacetylate and translocate to the cytoplasm, resulting in disruption of autophagic flux, impaired cholesterol uptake and deficient testosterone biosynthesis . Another study in 2021 demonstrated that autophagic flux and autophagy-mediated testosterone synthesis are defective in SF1-Sirt1−/− mice. In 2019, an elegant study described autophagy-dependent steroid hormone (ecdysone) production in the Drosophila model by demonstrating that autophagy mediates lipid trafficking required for steroid synthesis . A Representative confocal images of the luteinized granulosa cells of the patients with normal and defective luteal function treated with hCG (10 IU/ml) w/wo chloroquine (CQ, 60 μM). Defective co-localization of BODYPY with lysosome became more obvious in the cells with defective LF when they were treated with an hCG+chloroquine combination (Fig. 8A, B, Supplementary Fig. S6 and Supplementary Movies S5 and S6) in comparison to the control cells with normal LF.
+M6A induces the decay of the Camkk2 transcript in Leydig cells (LCs). As expected, knock down of YTHDF1 resulted in lower PPM1A protein levels, while we observed no significant changes in mRNA (Figure 7A–C and S14A-C). Because m6A methylation appeared to reduce the expression of CAMKK2, we speculated that the Camkk2 transcript was a target of YTHDF2, a protein that is capable of reducing the stability of m6A methylated transcripts. (F) TM3 cells were transfected with pcDNA3.1-Alkbh5 (O/E Alkbh5) before transfection with pcDNA3.1-Ppm1a (O/E Ppm1a), and cell lysate was subjected to western blotting and quantitative analysis.
+Moreover, these conditions are further characterized by higher levels of reactive oxygen species (ROS) and impaired mitochondria function. These effects can be counteracted by inhibiting autophagy (Ma et al., 2018). Additionally, brief exposure to hypoxia leads to a reduction in LD size and quantity but fosters an increase in [buy testosterone online](https://gaiaathome.eu/gaiaathome/show_user.php?userid=1895881) release (Figure 3C). This mechanism not only helps with the recycling of cellular components but also contributes to the liberation of essential building blocks such as free fatty acids (Khawar et al., 2019; Khawar et al., 2021a). These findings indicate that the autophagy-lysosome pathway breaks down the Na+/H+ exchanger regulatory factor 2 (NHERF2), which functions as a suppressor of SR-BI.
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