Pathophysiologic Mechanisms of Insulin Secretion and Signaling-Related Genes in Etiology of Polycystic Ovary Syndrome

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women. PCOS is characterized by anovulation, hyperandrogenism, polycystic ovaries, insulin resistance, and obesity. Despite the finding that the genetic origin of PCOS is well demonstrated in previous twin and familial clustering studies, genes and factors that can exactly explain the PCOS pathophysiology are not known. Objective(s). In this review, we attempted to identify genes related to secretion and signaling of insulin aspects of PCOS and their physiological functions in order to explain the pathways that are regulated by these genes which can be a prominent function in PCOS predisposition. Materials and Methods. For this purpose, published articles and reviews dealing with genetic evaluation of PCOS in women from peer-reviewed journals in PubMed and Google Scholar databases were included in this review. Results. The genomic investigations in women of different populations identified many candidate genes and loci that are associated with PCOS. The most important of them are INSR, IRS1-2, MTNR1A, MTNR1B, THADA, PPAR-γ2, ADIPOQ, and CAPN10. These are mainly associated with metabolic aspects of PCOS. Conclusions. In this review, we proposed that each of these genes may interrupt specific physiological pathways by affecting them and contribute to PCOS initiation. It is clear that the role of genes involved in insulin secretion and signaling is more critical than other pathways.

Case Report:Pregnancy and birth in a mild phenotype of Alström syndrome

“…The mild phenotype of this AS patient without IR or obesity, associated only with a mild initial increase of androgen levels, may have spared the patient's fertility and led to the possibility of a spontaneous conception. In fact, it is well known from PCOS studies that IR and hyperinsulinemia influenced fertility and conception, enhancing androstenedione and testosterone production, reducing SHBG levels, increasing free testosterone levels, stopping follicles growth, influencing pituitary gland sensitivity to GnRH, and stimulating pituitary LH release ( Shaaban et al, 2021 ). A recent study in mice suggests a direct role of ALMS1 on fertility.…”

Efficacy of metformin in treating polycystic ovarian syndrome among women: A observational study

“…Obesity as a risk factor often causes female ~ 109 ~ diseases such as breast cancer [17] . Studies have found that, with increases in weight, abnormal genes such as the Wnt signaling pathway, oxidative stress, and inflammation in adipose tissue of PCOS patients are abnormal [18] , suggesting that obesity participates in the pathogenesis of PCOS [19] , triggers metabolic and reproductive disorders, and may also cause glycolipid metabolism, hyperandrogenaemia, menstrual disorders, infertility, and comorbidities related to polycystic ovary syndrome [20] . Furthermore, we also noticed that many features and complications of polycystic ovary syndrome (PCOS) can trigger oxidative stress and increase insulin resistance index [21,22] .…”

Metabolic and Molecular Mechanisms of Diet and Physical Exercise in the Management of Polycystic Ovarian Syndrome

“…The genetic predisposition in PCOS is unquestionable and several genes are demonstrated to be involved in the etiology of the disease [ 25 ]. Indeed, due to the multifactorial nature of this disease, and to its polygenic contributions, it is not easy to offer a complete report about the genetic basis of PCOS [ 26 ].…”