Abstract：
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age and is a significant cause of female subfertility. Our previous research demonstrated that the abnormal palmitoylation of heat shock protein-90α (HSP90α) plays a role in the development of PCOS. However, the palmitoyl acyltransferases in HSP90α palmitoylation remain poorly understood. Herein, we identified ZDHHC17 as a major palmitoyl acyltransferase for HSP90α palmitoylation in granulosa cells. ZDHHC17 protein expression was diminished under excess androgen conditions in vitro and in vivo. Consistently, ovarian ZDHHC17 expression was found to be attenuated in patients with PCOS. ZDHHC17 depletion decreased HSP90α palmitoylation levels and hampered the conversion of androgen to estrogen via CYP19A1. Furthermore, ZDHHC17-mediated regulation of CYP19A1 expression was dependent on HSP90α palmitoylation. Our findings reveal that the regulatory role of HSP90α palmitoylation by ZDHHC17 is critical in PCOS pathophysiology and provide insights into the role of ZDHHC17 in reproductive endocrinology.
摘要：
多囊卵巢综合征（PCOS）是影响育龄女性的常见内分泌疾病，是女性不孕症的重要原因。我们先前的研究表明，热休克蛋白-90α（HSP90α）的异常棕榈酰化在PCOS的发生发展中起作用。然而,HSP90α棕榈酰化中的棕榈酰基转移酶仍然知之甚少。在这里，我们确定ZDHHC17是颗粒细胞中HSP90α棕榈酰化的主要棕榈酰基转移酶。ZDHHC17蛋白表达在体外和体内过量雄激素条件下减少。始终如一，发现PCOS患者卵巢ZDHHC17表达减弱。ZDHHC17的消耗降低了HSP90α棕榈酰化水平，并阻碍了雄激素通过CYP19A1向雌激素的转化。此外，ZDHHC17介导的CYP19A1表达调控依赖于HSP90α棕榈酰化。我们的发现表明，ZDHHC17对HSP90α棕榈酰化的调节作用在PCOS病理生理学中至关重要，并为ZDHHC17在生殖内分泌学中的作用提供了见解。
