Neurotransmitter, neuropeptide and gut peptide profile in PCOS-pathways contributing to the pathophysiology, food intake and psychiatric manifestations of PCOS.

Polycystic ovary syndrome (PCOS) is a major health problem with a heterogeneous hormone-imbalance and clinical presentation across the lifespan of women. Increased androgen production and abnormal gonadotropin-releasing hormone (GnRH) release and gonadotropin secretion, resulting in chronic anovulation are well-known features of the PCOS. The brain is both at the top of the neuroendocrine axis regulating ovarian function and a sensitive target of peripheral gonadal hormones and peptides. Current literature illustrates that neurotransmitters regulate various functions of the body, including reproduction, mood and body weight. Neurotransmitter alteration could be one of the reasons for disturbed GnRH release, consequently directing the ovarian dysfunction in PCOS, since there is plenty evidence for altered catecholamine metabolism and brain serotonin or opioid activity described in PCOS. Further, the dysregulated neurotransmitter and neuropeptide profile in PCOS could also be the reason for low self-esteem, anxiety, mood swings and depression or obesity, features closely associated with PCOS women. Can these altered central brain circuits, or the disrupted gut-brain axis be the tie that would both explain and link the pathogenesis of this disorder, the occurrence of depression, anxiety and other mood disorders as well as of obesity, insulin resistance and abnormal appetite in PCOS? This review intends to provide the reader with a comprehensive overview of what is known about the relatively understudied, but very complex role that neurotransmitters, neuropeptides and gut peptides play in PCOS. The answer to the above question may help the development of drugs to specifically target these central and peripheral circuits, thereby providing a valuable treatment for PCOS patients that present to the clinic with GnRH/LH hypersecretion, obesity or psychiatric manifestations.

Advances in PCOS Pathogenesis and Progression-Mitochondrial Mutations and Dysfunction.

Polycystic ovary syndrome (PCOS) is a common female endocrine disorder, which still remains largely unsolved in terms of etiology and pathogenesis despite important advances in our understanding of its genetic, epigenetic, or environmental factor implications. It is a heterogeneous disease, frequently associated with insulin resistance, chronic inflammation, and oxidative stress and probably accompanied with subclinical cardiovascular disease (CVD) and some malignant lesions as well, such as endometrial cancer. Discrepancies in the clinical phenotype and progression of PCOS exist between different population groups, which nuclear genetic studies have so far failed to explain. Over the last years, mitochondrial dysfunction has been increasingly recognized as an important contributor to an array of diseases. Because mitochondria are under the dual genetic control of both the mitochondrial and nuclear genomes, mutations within either DNA molecule may result in deficiency in respiratory chain function that leads to a reduced ability to produce cellular adenosine-5'-triphosphate and to an excessive production of reactive oxygen species. However, the association between variants in mitochondrial genome, mitochondrial dysfunction, and PCOS has been investigated to a lesser extent. May mutations in mitochondrial DNA (mtDNA) become an additional target of investigations on the missing PCOS heritability? Are mutations in mtDNA implicated in the initiation and progression of PCOS complications, e.g., CVDs, diabetes mellitus, cancers?

Polycystic Ovary Syndrome-Epigenetic Mechanisms and Aberrant MicroRNA.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age affecting various functions including reproduction and metabolism. This syndrome is associated with increased prevalence of subclinical cardiovascular disease as well as endometrial and ovarian cancer. This syndrome is highly heterogeneous and it is not yet clear which factors are responsible for the development of a particular phenotype. Current research has shown that the interaction of susceptible and protective genomic variants under the influence of environmental factors can modify the clinical presentation via epigenetic modifications. MicroRNA (miRNA) are regulators of gene expression. Altered miRNA expression has been associated with various diseases such as diabetes, insulin resistance, inflammation, and cancer. Several miRNA have been identified in PCOS. This review examines the role of epigenetics and miRNA in the pathophysiology of this complex disease process.