Sex hormone binding globulin as a potential drug candidate for liver-related metabolic disorders treatment

Bourebaba, Nabila; Ngo, ThuHa; Śmieszek, Agnieszka; Bourebaba, Lynda; Marycz, Krzysztof

doi:10.1016/j.biopha.2022.113261

Cited by 32 publications

(29 citation statements)

References 56 publications

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“…17,18 Besides, oral contraceptives can significantly increase SHBG levels in females 19 ; in males, SHBG levels decrease in the presence of obesity or diabetes. 9 Study has found that SHBG levels in women with major depression are not significantly altered, 20 which is consistent with the finding in this study that there is no causal relationship between SHBG and major depression in women. Some studies have found a potential relationship between sex hormones and major depression.…”

Section: Discussionsupporting

confidence: 88%

“…7 Clinical research has found that changes in SHBG levels are associated with metabolic syndrome and cardiovascular diseases. 8,9 It was found that there is a certain correlation between SHBG and cognitive impairment in patients with schizophrenia accompanied by depression, but there are almost no studies directly investigating the relationship between SHBG and depression. 10 Mendelian randomization (MR) is a technique that uses genetic variation as an auxiliary tool to evaluate the causal relationship between risk factors and specific diseases.…”

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confidence: 99%

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Causal relationship between sex hormone‐binding globulin and major depression: A Mendelian randomization study

Zhu,

Sun,

Guo

et al. 2023

Acta Psychiatr Scand

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ObjectiveThis study aimed to explore the causal relationship between sex hormone‐binding globulin (SHBG) and major depression using two‐sample Mendelian randomization (MR) studies.MethodsBased on the genome‐wide association study (GWAS) summary data of SHBG and major depression in the European population, which included 214,989 female SHBG samples, 185,221 male SHBG samples, and 500,199 major depression samples, we used genetic factors as instrumental variables to conduct two‐sample MR analyses. We used methods including inverse variance weighted (IVW), weighted median, weighted mode, and MR Egger to evaluate the bidirectional causal relationship between SHBG and major depression.ResultsThe results showed that there was a causal relationship between female SHBG and major depression, which was positively correlated. The ORs were 1.056 (95% CI: 1.005–1.109, p = 0.031) for the weighted median and 1.067 (95% CI: 1.012–1.126, p = 0.021) for the weighted mode. There was no significant effect of male SHBG on major depression (p > 0.05), and there was no significant effect of major depression on female SHBG (p > 0.05). Major depression was negatively correlated with male SHBG, indicating that major depression could lead to a decrease in male SHBG. The OR was 0.954 (95% CI: 0.916–0.993, p = 0.023) for IVW.ConclusionFemale SHBG was positively correlated with the risk of major depression, however, major depression was found to be negatively correlated with serum SHBG levels in men, indicating that SHBG plays distinct roles in patients with major depression of different genders.

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Section: Discussionsupporting

confidence: 88%

mentioning

confidence: 99%

Causal relationship between sex hormone‐binding globulin and major depression: A Mendelian randomization study

Zhu,

Sun,

Guo

et al. 2023

Acta Psychiatr Scand

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“…SHBG is a glycoprotein synthesized by hepatocytes that has high affinity with steroid hormones and can regulate the concentration of sex hormones and affect their activity. 29 SHBG is widely used in the diagnosis of obstetric diseases, precocious puberty, breast development, pregnancy-induced hypertension, diabetes and thyroid disease. 30 As SHBG is quite related to the biological functions of each sex hormone, our data provide a clue for advanced application of SHBG in CSC management.…”

Section: Discussionmentioning

confidence: 99%

The Association Between Circulating Sex Hormones and Central Serous Chorioretinopathy: A Case-Control Study

Zhao¹,

Huang²,

Chen³

et al. 2022

TCRM

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Background: Central serous chorioretinopathy (CSC) is preferential cocurated in males, however the associations between sex hormones and CSC incidence or progression remains unclear. The sex hormone concentration assessments in CSC cases and healthy controls will update the knowledge in CSC management. Methods: This case-control study included 59 CSC cases and 30 healthy controls, from January 2019 to December 2020. The CSC cases would be defined as spontaneous resolved if the subretinal fluid were absorbed within three months. The concentrations of total testosterone (TT), free testosterone (FT), estradiol (E2), sex hormone-binding globulin (SHBG), progesterone, leuteinizing hormone (LH) and dehydroepiandrosterone sulfate (DHEA-S) were detected in all the participants. The relationships between sex hormone concentrations and CSC-related characteristics were analyzed with Pearson correlation analyses. Results: Significantly increased TT, FT, FT/E2 ratio, SHBG concentrations as well as decreased DHEA-S level were detected in nonresolved CSC group compared with the control group. Comparing with the resolved ones, it was found that TT, FT and SHBG concentrations were increased in the non-resolved CSC. A significant positive correlation between TT concentrations and CMT (R 2 =0.168, P=0.031) as well as SRF height (R 2 =0.146, P=0.045) were detected in the non-solved CSC group. Conclusion: Different concentrations of TT, FT, FT/E2 ratio, DHEA-S and SHBG were detected in resolved and non-resolved CSC cases. Sex hormones were related to CSC symptom durations and related parameters.

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“…During chronic inflammation diseases, patients show increased expression of inflammatory cytokines such as IL-1 and TNF-α that affect the production of SHBG. The action of IL-1 is mediated by the NF-κB factor which downregulate HNF-4 α transcription leading to the suppression of SHGB synthesis ( 94 ).…”

Section: Sex Hormone Binding Globulin Status In the Course Of Nafldmentioning

confidence: 99%

Androgen dysfunction in non-alcoholic fatty liver disease: Role of sex hormone binding globulin

Song

Choi

2022

Front. Endocrinol.

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Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in the world. It is linked mainly to insulin resistance and metabolic syndrome including obesity and dyslipidemia. In addition, various endocrine dysfunctions including polycystic ovary syndrome (PCOS) and hypogonadism are involved in the development and progression of NAFLD. We need to know the disease pathophysiology more accurately due to the heterogeneity of clinical presentation of fatty liver disease. The liver is the major metabolic organ with sexual dimorphism. Sexual dimorphism is associated not only with behavioral differences between men and women, but also with physiological differences reflected in liver metabolism. In men, normal androgen levels prevent hepatic fat accumulation, whereas androgen deficiency induce hepatic steatosis. In women, higher androgens can increase the risk of NAFLD in PCOS. Sex hormone binding globulin (SHBG) is involved in androgen regulation. Recently, SHBG may be reported as a surrogate marker for NAFLD. Therefore, this review will focus on the mechanism of androgen dysfunction in the regulation of hepatic metabolism, the risk of developing NAFLD, and the potential role of SHBG in the course of NAFLD.; Keywords: Non-alcoholic fatty liver disease, insulin resistance, sexual dimorphism, androgen, sex hormone binding globulin

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Sex hormone binding globulin as a potential drug candidate for liver-related metabolic disorders treatment

Cited by 32 publications

References 56 publications

Causal relationship between sex hormone‐binding globulin and major depression: A Mendelian randomization study

Causal relationship between sex hormone‐binding globulin and major depression: A Mendelian randomization study

The Association Between Circulating Sex Hormones and Central Serous Chorioretinopathy: A Case-Control Study

Androgen dysfunction in non-alcoholic fatty liver disease: Role of sex hormone binding globulin

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