Rajashekara Nitin K, Jayashankaraswamy Bindu, Nataraj Raghu
Division of Molecular Biology, School of Life Sciences, JSS Academy of Higher Education and Research, Mysuru, India.
Department of Biotechnology, Sri Jayachamarajendra College of Engineering, JSS Science and Technology University, Mysuru, India.
Neuroendocrinology. 2025 Apr 26:1-15. doi: 10.1159/000546126.
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 the PCOS condition. This contradiction has led to several independent research studies assessing the role of metastatic suppressor genes Kisspeptin (KiSS1) and Insulin (INS2) in regulating LH by acting upon GnRH. The current study demonstrates the coexpressive role of KiSS1 and INS2 in regulating LH and monitoring ovarian health.
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.
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, 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.
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 preclinical Rattus norvegicus models.
多囊卵巢综合征（PCOS）是正常卵巢功能的一种异常表现，会阻碍卵泡生成。临床上，被诊断为PCOS的患者存在慢性心理困扰，在皮质醇的影响下下丘脑 - 垂体 - 性腺（HPG）轴功能下调，但与此相反，其他地方进行的研究表明在PCOS情况下下丘脑 - 垂体活动增加。这种矛盾导致了几项独立的研究，评估转移抑制基因亲吻素（KiSS1）和胰岛素（INS2）通过作用于促性腺激素释放激素（GnRH）来调节促黄体生成素（LH）的作用。当前研究证明了KiSS1和INS2在调节LH和监测卵巢健康方面的共表达作用。
通过慢性应激方案在大鼠中诱导出PCOS样特征，并确定相关参数。另一组应激动物在应激暴露前给予60mg/kg体重的酮康唑，然后评估并确定研究参数。
当前研究观察到，在慢性应激暴露后，动物表现出了PCOS的所有特征，如高雄激素血症、卵泡囊肿伴发情周期失调、LH升高和血浆胰岛素水平降低。正如所假设的，在应激组动物中观察到KiSS1表达增加了7倍，INS - 2表达增加了2倍，而皮质酮抑制剂组动物表现出可控的表型。
KiSS1和INS2基因表达水平获得的相对倍数变化揭示了应激通过神经内分泌调节与PCOS病理之间的关联。该研究证明了在临床前褐家鼠模型中存在由KiSS1 - INS2表达驱动的LH升高的假定时间偶联活性。
