This study investigated the potential effect of adrenomedullin (ADM) on metabolic and endocrinal dysfunctions in experimentally induced polycystic ovary. Twenty‐four female Wistar rats were allocated into three groups: control; polycystic ovary syndrome (PCOS) in which PCOS was induced by letrozole, orally in a dose of 1 mg/kg once daily for 3 weeks; and ADM group in which ADM was injected intraperitonally in a dose of 3.5/μg/twice daily for 4 weeks. At the end of the experimental period, the serum sex hormone profile, ADM, fasting glucose, insulin, homeostatic model assessment of insulin resistance, and lipid parameters were determined. Ovarian tissue homogenates were used to determine malondialdehyde, total antioxidant capacity, glutathione peroxidase activity, tumor necrosis factor α, interleukin 6, B cell lymphoma‐2 (Bcl‐2), and Bcl‐2 associated X protein. The profibrotic growth factors, including transforming growth factor β1 and connective tissue growth factor, were determined; and also, the relative gene expression of endoplasmic reticulum (ER) stress, including (Xbox‐binding protein‐1 [XBP‐1], activating transcription factor 6 [ATF6], and homologous protein [CHOP]), serine/threonine kinase 1 (Akt1), phosphatidylinositol 3‐kinase (PI3K), and peroxisome proliferator‐activated receptor γ (PPAR‐γ) were determined. Finally, histopathological analysis of the ovaries was evaluated. PCOS group exhibited increased ER stress, suppressing of PI3K/Akt1 and PPAR‐γ pathways, imbalance of sex hormonal profile, hyperglycemia, insulin resistance, dyslipidemia, increased profibrotic factors, and abnormal ovarian histopathological picture, while ADM treatment alleviated these disturbances occurring in the PCOS model. We concluded that ADM mitigated PCOS via attenuating the ER stress, in addition to activation of PI3K/Akt1 and PPAR‐γ pathways, its antioxidant, anti‐inflammatory, antiapoptotic, and antifibrotic properties.

中文翻译：

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肾上腺髓质素对实验诱导的多囊卵巢的代谢和内分泌功能障碍的潜在影响：内质网应激的目标暗示。

这项研究调查了肾上腺髓质素（ADM）对通过实验诱导的多囊卵巢代谢和内分泌功能障碍的潜在影响。将二十四只Wistar雌性大鼠分为三组：对照组；对照组；和对照组。多囊卵巢综合征（PCOS），其中曲乐唑口服PCOS以1 mg / kg的剂量口服，持续3周；ADM组，腹膜内注射ADM，剂量为每天3.5 /μg/两次，连续4周。在实验期结束时，确定了血清性激素谱，ADM，空腹血糖，胰岛素，胰岛素抵抗的稳态模型评估和脂质参数。卵巢组织匀浆用于测定丙二醛，总抗氧化能力，谷胱甘肽过氧化物酶活性，肿瘤坏死因子α，白介素6，B细胞淋巴瘤2（Bcl-2），和Bcl-2相关的X蛋白。确定了原纤维化生长因子，包括转化生长因子β1和结缔组织生长因子。以及内质网应激的相对基因表达，包括（Xbox结合蛋白-1 [XBP-1]，激活转录因子6 [ATF6]和同源蛋白[CHOP]），丝氨酸/苏氨酸激酶1 （Akt1），磷脂酰肌醇3激酶（PI3K）和过氧化物酶体增殖物激活的受体γ（PPAR-γ）被确定。最后，评估卵巢的组织病理学分析。PCOS组表现出ER应激增加，PI3K / Akt1和PPAR-γ通路抑制，性激素谱失衡，高血糖，胰岛素抵抗，血脂异常，纤维化因子增加以及卵巢组织病理学异常，而ADM处理则减轻了PCOS模型中发生的这些干扰。我们得出的结论是，ADM除了通过激活PI3K / Akt1和PPAR-γ途径，其抗氧化，抗炎，抗凋亡和抗纤维化特性外，还可以通过减轻ER应力来缓解PCOS。