Existence of co-expressive role of Kisspeptin and Insulin-2 in the regulation of Luteinizing hormone (LH) in chronic stress-induced polycystic ovarian syndrome (PCOS)-like phenotype in Rattus norvegicus

Background: Polycystic ovary syndrome (PCOS) is an ill manifestation of the normal ovarian function that obstructs folliculogenesis. Clinically, patients diagnosed with PCOS possess chronic psychological distress with the downregulated hypothalamus-pituitary-gonadal (HPG) axis under the influence of cortisol, but, in contrast, studies done elsewhere have demonstrated an increased hypothalamus-pituitary activity under PCOS condition. This contradiction has led to several independent research studies assessing the role of metastatic suppressor gene Kisspeptin (KISS1), and Insulin (INS2) in regulating LH by acting upon GnRH. The current study demonstrates the co-expressive role of KiSS1 and INS2 in regulating LH and monitoring ovarian health. Methodology: PCOS-like features were induced in the rats by a chronic stress regime, and the parameters were established. Another stress group of animals was dosed with 60 mg/kg body weight of ketoconazole before the stress exposure, and the parameters of the study were estimated and established. Results: The current study has observed that upon chronic stress exposure, the animals have exhibited all the features of PCOS like hyperandrogenism, cystic follicles with dysregulated estrous cyclicity, along with, an elevated LH, and decreased plasma insulin levels. As hypothesized, a 7-fold increase of KiSS1 expression and a 2-fold increase of INS-2 expressions have been observed in the stress group animals unlike the corticosterone inhibitor group of animals which have exhibited a controlled phenotype. Conclusion: The obtained relative fold changes in the gene expression level of both KiSS1 and INS2 reveal the association of stress with the pathology of PCOS via neuroendocrine regulation. The study has demonstrated the existence of a putative temporal coupling activity of KiSS1-INS2 expression-driven elevated LH in pre-clinical Rattus norvegicus models.