Mitochondrial Dysfunction in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common female reproductive metabolisms. It is an endocrine disease that affects reproductive women and often exhibits with hyperandrogenemia, insulin resistance (IR), low inflammation, and an increased risk of type 2 diabetes mellitus, metabolic syndrome, and cardiovascular events such as hypertension and dyslipidemia in patients. However, the molecular mechanism of PCOS is still unclear. Recently, an increasing number of studies have shown that the oxidative stress induced by mitochondrial dysfunction has negative effects on IR, lipid metabolism, and follicular development, suggesting that mitochondrial dysfunction plays an essential role in the development of PCOS. Abnormal mitochondrial DNA copy number in patients with PCOS, and mitochondrial gene mutations, has been the focus of research in recent years, and functional mitochondrial diseases have been gradually accepted as a related factor in PCOS. This review is intended to summarize and discuss previous and recent studies and findings on the connections between mitochondrial dysfunction and PCOS.

Polycystic ovarian syndrome: Correlation between hyperandrogenism, insulin resistance and obesity.

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disease characterized by clinical or laboratorial hyperandrogenism, oligo-anovulation and metabolic abnormalities, including insulin resistance, excessive weight or obesity, type II diabetes, dyslipidemia and an increased risk of cardiovascular disease. The most significant clinical manifestation of PCOS is hyperandrogenism. Excess androgen profoundly affects granulosa cell function and follicular development via complex mechanisms that lead to obesity and insulin resistance. Most PCOS patients with hyperandrogenism have steroid secretion defects that result in abnormal folliculogenesis and failed dominant follicle selection. Hyperandrogenism induces obesity, hairy, acne, and androgenetic alopecia. These symptoms can bring great psychological stress to women. Drugs such as combined oral contraceptive pills, metformin, pioglitazone and low-dose spironolactone help improve pregnancy rates by decreasing androgen levels in vivo. Notably, PCOS is heterogeneous, and hyperandrogenism is not the only pathogenic factor. Obesity and insulin resistance aggravate the symptoms of hyperandrogenism, forming a vicious cycle that promotes PCOS development. Although numerous studies have been conducted, the definitive pathogenic mechanisms of PCOS remain uncertain. This review summarizes and discusses previous and recent findings regarding the relationship between hyperandrogenism, insulin resistance, obesity and PCOS.

Sex hormone-binding globulin and polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS), one of the most common endocrine diseases that causes infertility in reproductive women, is characterized by hyperandrogenemia, chronic anovulation, and polycystic ovary morphology (PCOM), and most women with PCOS have metabolic abnormalities. A reduction in plasma sex hormone-binding globulin (SHBG), a transport carrier that binds estrogen and androgens and regulates their biological activities, is often used as an indicator of hyperandrogenism in women with PCOS. Low serum SHBG levels are considered a biomarker of abnormal metabolism and are related to insulin resistance (IR), compensatory hyperinsulinemia and abnormalities in glucose and lipid metabolism in PCOS patients. SHBG is also associated with the long-term prognosis of PCOS. SHBG gene polymorphism is correlated with the risk of PCOS. As SHBG plays a vital role in the occurrence and development of PCOS, knowledge regarding its role in PCOS is helpful for further understanding the molecular mechanism of SHBG in PCOS development and providing new ideas for the treatment of female infertility. Hepatocyte nuclear factor-4α (HNF-4α) is a vital transcription factor in the SHBG synthesis process. HNF-4α binds to the cis-type element DR1 in the SHBG promoter to initiate transcription and regulates hepatic SHBG levels by modulating glucose and lipid metabolism and inflammatory factors. However, it remains unclear whether HNF-4α is indirectly involved in the pathogenesis of PCOS via regulation of hepatic SHBG synthesis. Therefore, this review discusses the interaction between SHBG and the various complications of PCOS as well as the regulatory effect of HNF-4α on SHBG expression.

Nogo­B receptor in relevant carcinoma: Current achievements, challenges and aims (Review).

The novel neurite outgrowth inhibitor B (Nogo­B) receptor (NgBR) is specific for Nogo­B, which is highly expressed in various human organs and cells, including the lung, liver, kidney, smooth muscle cells, blood vessel endothelial cells and inflammatory cells. Previous studies have indicated that NgBR directly interacts with Nogo­B and is able to independently influence lipid and cholesterol homeostasis, angiogenesis, N­glycosylation, the epithelial-mesenchymal transition, the chemotaxis of endothelial cells and cellular proliferation and apoptosis. These multiple functions and actions of this receptor provide an understanding of the important roles of NgBR in various conditions, including fatty liver, atherosclerosis, intracranial microaneurysms, retinitis pigmentosa and severe neurological impairment. Furthermore, NgBR has been demonstrated to exert protean, multifunctional and enigmatic effects in cancer. The present review summarizes the latest knowledge on the suppressing and activating effects of NgBR, emphasizing its function in cancer. Further basic and medical research on this receptor may provide novel insight into its clinical implications on the prognosis of relevant human cancer types.

Neurite Outgrowth Inhibitor B Receptor: A Versatile Receptor with Multiple Functions and Actions.

Members of the reticulon protein family are predominantly distributed within the endoplasmic reticulum. The neurite outgrowth inhibitor (Nogo) has three subtypes, including Nogo-A (200 kDa), Nogo-B (55 kDa), and Nogo-C (25 kDa). Nogo-A and Nogo-C are potent Nogos that are predominantly expressed in the central nervous system. Nogo-B, the splice variant of reticulon-4, is expressed widely in multiple human organ systems, including the liver, lung, kidney, blood vessels, and inflammatory cells. Moreover, the Nogo-B receptor (NgBR) can interact with Nogo-B and can independently affect nervous system regeneration, the chemotaxis of endothelial cells, proliferation, and apoptosis. In recent years, it has been demonstrated that NgBR plays an important role in human pathophysiological processes, including lipid metabolism, angiogenesis, N-glycosylation, cell apoptosis, chemoresistance in human hepatocellular carcinoma, and epithelial-mesenchymal transition. The pathophysiologic effects of NgBR have garnered increased attention, and the detection and enhancement of NgBR expression may be a novel approach to monitor the development and to improve the prognosis of relevant human clinical diseases.