CYP19A1 gene expression in patients with polycystic ovarian syndrome

Panghiyangani, Roselina; Soeharso, Purnomo; Andrijono,; Suryandari, Dwi Anita; Wiweko, Budi; Kurniati, Mala; Pujianto, Dwi Ari

doi:10.4103/jhrs.jhrs_142_18

Cited by 25 publications

(12 citation statements)

References 19 publications

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“…A prospective crosssectional study showed that IR secondary to PCOS insulinmediated decreased glucose uptake and increased insulin secretion was partly due to decreased GLUT4 expression in adipocytes without a compensatory increase in GLUT1 expression (34). The analysis of signaling components of the IRS/PI3K/AKT pathway showed that the expression of GLUT4 was significantly decreased in PCOS patients and the IR control group (35). Their results point to a new mechanism by which miR-93 regulates insulin-stimulated glucose uptake and demonstrates that the upregulated expression of miR-93 in all women with IR with or without PCOS may be the cause of IR in this syndrome.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D deficiency inhibits microRNA-196b-5p which regulates ovarian granulosa cell hormone synthesis, proliferation, and apoptosis by targeting RDX and LRRC17

Wan¹,

Sun²,

Mao³

et al. 2021

Ann Transl Med

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Background: In polycystic ovary syndrome (PCOS), ovarian physiology is tightly linked to the metabolic disturbances observed in this disease. Vitamin D (VD) plays an important role in the regulation of ovulatory dysfunction and can influence genes involved in steroidogenesis in granulosa cells (GCs). However, its role in the proliferation and apoptosis of ovarian GCs is unclear. The present study aimed to investigate the role of in the hormone synthesis, proliferation, and apoptosis of ovarian GCs. Methods:The abnormal expression of miRNAs in ovarian tissues of VD-deficient mice was analyzed using transcriptome sequencing. The direct target of miR-196b-5p was predict and confirmed by bioinformatics analysis and the dual-luciferase reporter assay. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect the levels of miR-196b-5p, cell proliferation was detected via the CCK8 assay, and cell apoptosis and reactive oxygen species (ROS) were measured via flow cytometry. The levels of radixin (RDX), leucine rich repeat containing 17 (LRRC17), aromatase (CYP19A1), and glucose transporter 4 (GLUT4) were detected by performing RT-qPCR or western blot.Results: We found that miR-196b-5p was significantly downregulated among the 672 miRNAs that were differentially expressed (DE) in VD-deficient mice. In addition, the results demonstrated that downregulated expression of miR-196b-5p significantly increased the level of RDX and LRRC17, and reduced expression of miR-196b-5p significantly promoted ovarian GC apoptosis and inhibited cell proliferation. Downregulated expression of miR-196b-5p promoted cellular ROS production and inhibited sex hormone production and glucose uptake. Transfection with miR-196b-5p mimics significantly increased the expression of CYP19A1 and GLUT4 and decreased the RDX and LRRC17 levels in ovarian GCs. Conclusions:This study shows that miR-196b-5p can regulate the oxidative stress (OS), glucose uptake, and steroid production pathway of GCs, thus promoting follicular development and maturation. This is a step towards a feasible treatment for PCOS.

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Section: Discussionmentioning

confidence: 99%

Vitamin D deficiency inhibits microRNA-196b-5p which regulates ovarian granulosa cell hormone synthesis, proliferation, and apoptosis by targeting RDX and LRRC17

Wan¹,

Sun²,

Mao³

et al. 2021

Ann Transl Med

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“…Data on the influence of the inflammatory response on the production of androgens as a result of posttranscriptional regulation of gene expression in PCOS are being constantly updated [ 209 , 213 , 214 ]. Thus, any epigenetic regulation that leads to a decrease in the expression of the CYP19A1 (aromatase) gene in granulosa cells or a decrease in the relative expression rate of GC aromatase, as well as producing upregulation of AR and increased activity of the key enzymes essential for androgen biosynthesis in thecal cells (i.e., CYP11A1, CYP17, and HSD3B2), should be considered in the context of inflammation in PCOS [ 211 , 215 , 216 , 217 ] ( Figure 3 ).…”

Section: Epigenetic Modulation Of Androgenic Activity In Response To ...mentioning

confidence: 99%

Modulation of the Inflammatory Response in Polycystic Ovary Syndrome (PCOS)—Searching for Epigenetic Factors

Szukiewicz

Trojanowski

Kociszewska

et al. 2022

IJMS

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Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Despite its incidence, the syndrome is poorly understood and remains underdiagnosed, and female patients are diagnosed with a delay. The heterogenous nature of this complex disorder results from the combined occurrence of genetic, environmental, endocrine, and behavioral factors. Primary clinical manifestations of PCOS are derived from the excess of androgens (anovulation, polycystic ovary morphology, lack of or scanty, irregular menstrual periods, acne and hirsutism), whereas the secondary manifestations include multiple metabolic, cardiovascular, and psychological disorders. Dietary and lifestyle factors play important roles in the development and course of PCOS, which suggests strong epigenetic and environmental influences. Many studies have shown a strong association between PCOS and chronic, low-grade inflammation both in the ovarian tissue and throughout the body. In the vast majority of PCOS patients, elevated values of inflammatory markers or their gene markers have been reported. Development of the vicious cycle of the chronic inflammatory state in PCOS is additionally stimulated by hyperinsulinemia and obesity. Changes in DNA methylation, histone acetylation and noncoding RNA levels are presented in this review in the context of oxidative stress, reactive oxygen species, and inflammatory signaling in PCOS. Epigenetic modulation of androgenic activity in response to inflammatory signaling is also discussed.

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“…In granulosa cells, SF-1 can bind to the cAMP response element and act on aromatase promoter II, thereby causing estrogen production ( 101 ). Abnormally expressed SF-1 in endometriosis will compete with the aromatase expression inhibitor-chicken ovalbumin upstream promoter-transcription factor (COUP-TF) for the same binding site, thereby stimulating the activity of aromatase P450 ( 102 ). Moreover, glucocorticoids and IL1βcan affect the secretion of estrogen by regulating the expression of aromatase promoter 1.4, thereby affecting the occurrence of uterine fibroids ( 103 ).…”

Section: Changes In Aromatase Activity Of Gcs Induce Diseasesmentioning

confidence: 99%

“…When androgen secretion is excessive, the high sensitivity of GCs to FSH causes a large increase in AMH, and AMH in turn inhibits the effect of FSH on aromatase in follicles ( 106 ). Recently, Che et al ( 107 ) found that the highly expressed lncRNA HUPCOS of granulosa cells in patients with PCOS can interact with RNA-binding protein with multiple splicing (RBPMS) and inhibit the expression of aromatase, thereby mediating the excess of androgen in the follicular fluid of PCOS patients Therefore, the decrease in the aromatase activity conversely helps maintain high androgen levels ( 102 , 107 ). In addition, CYP19A1 and A-Kinase anchor protein 95 (AKAP95) levels are significantly decreased in human luteinized GCs of patients with PCOS.…”

Section: Changes In Aromatase Activity Of Gcs Induce Diseasesmentioning

confidence: 99%

Estrogen disorders: Interpreting the abnormal regulation of aromatase in granulosa cells (Review)

2021

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Ovarian granulosa cells (Gcs) are the most important source of estrogen. Therefore, aromatase (estrogen synthase), which is the key enzyme in estrogen synthesis, is not only an important factor of ovarian development, but also the key to estrogen secretion by Gcs. disorders of the ovarian estrogen secretion are more likely to induce female estrogen-dependent diseases and fertility issues, such as ovarian cancer and polycystic ovary syndrome. Hence, aromatase is an important drug target; treatment with its inhibitors in estrogen-dependent diseases has attracted increasing attention. The present review article focuses on the regulation and mechanism of the aromatase activity in the Gcs, as well as the specific regulation of aromatase promoters. In GCs, follicle-stimulating hormone (FSH) is dependent on the cyclic adenosine monophosphate (cAMP) pathway to regulate the aromatase activity, and the regulation of this enzyme is related to the activation of signaling pathways, such as phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase (ERK). In addition, endocrine-disrupting substance and other related factors affect the expression of aromatase, which eventually create an imbalance in the estrogen secretion by the target tissues. The present review highlights these useful factors as potential inhibitors for target therapy.

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CYP19A1 gene expression in patients with polycystic ovarian syndrome

Cited by 25 publications

References 19 publications

Vitamin D deficiency inhibits microRNA-196b-5p which regulates ovarian granulosa cell hormone synthesis, proliferation, and apoptosis by targeting RDX and LRRC17

Vitamin D deficiency inhibits microRNA-196b-5p which regulates ovarian granulosa cell hormone synthesis, proliferation, and apoptosis by targeting RDX and LRRC17

Modulation of the Inflammatory Response in Polycystic Ovary Syndrome (PCOS)—Searching for Epigenetic Factors

Estrogen disorders: Interpreting the abnormal regulation of aromatase in granulosa cells (Review)

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