The upregulation of 11β-HSD1 in ovarian granulosa cells by cortisol and interleukin-1β in polycystic ovary syndrome

Abstract

Our previous study have demonstrated the elevated cortisol concentration in the follicular fluid (FF) contributed to the insulin resistance of the granulosa cells (GCs) in PCOS, but the complicated cortisol generation mechanisms are still unknown. 11β-hydroxysteroid type 1(11β-HSD1) mainly functions as reductase in intact cells, converting cortisone to cortisol. Cortisol and IL-1β are known to induce 11β-HSD1 in number of tissues, but few results were obtained in ovarian GCs In this study, FF and GCs from PCOS and non-PCOS patients were collected to study the interaction of cortisol and IL-1β in 11β-HSD1 expression. The ELISA and qRT-PCR revealed that the cortisol and IL-1β concentration in FF and 11β-HSD1 abundance in GCs were elevated in PCOS patients. By using cultured GCs in vitro, we demonstrated that both cortisol and IL-1β could stimulate 11β-HSD1 expression. The induction of 11β-HSD1 by IL-1β was further inducted by cortisol, whereas the induction of IL-1β and IL-6 expression by IL-1β was completely inhibited by cortisol. In conclusion, cortisol and IL-1β preformed a synergistically upregulation of 11β-HSD1 expression in GCs, contributing to the accumulation of cortisol in FF of PCOS patients. This may lead to the metabolic disorders of the ovary.

摘要

我们先前的研究证实卵泡液（FF）中皮质醇浓度升高是PCOS颗粒细胞（GCs）胰岛素抵抗的原因之一, 但其复杂的皮质醇生成机制尚不清楚。11β-羟基类固醇1（11β-HSD1）在完整细胞中主要作为还原酶, 将肾上腺皮质酮转化为皮质醇。皮质醇和IL-1β可在多种组织中诱导11β-HSD1的表达, 但在卵巢GCs中的研究结果很少。本研究收集PCOS患者和非PCOS患者的FF和GCs, 研究皮质醇和IL-1β在11β-HSD1表达中的相互作用。ELISA和qRT-PCR结果显示, PCOS患者FF中皮质醇和IL-1β浓度及GCs中11β-HSD1含量均升高。通过体外培养的GCs, 我们证明皮质醇和IL-1β都能刺激11β-HSD1的表达。皮质醇进一步促进IL-1β诱导11β-HSD1的表达, 而皮质醇完全抑制IL-1β和IL-6的诱导表达。总之, 皮质醇和IL-1β协同上调了GCs中11β-HSD1的表达, 促使了PCOS患者FF中皮质醇的积聚。这可能会导致卵巢的代谢紊乱。

The Chinese abstracts are translated by Prof. Dr. Xiangyan Ruan and her team: Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.

Keywords:

• 11β-HSD1
• cortisol
• granulosa cells
• IL-1β
• PCO

Disclosure statement

The authors declare no conflicts of interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [grant numbers 81801528, 81771648, 81571499]; the National Key R&D Program of China [grant number 2017YFC1001403]; the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant [grant number 20161413]; the Program of Shanghai Academic Research Leader in Shanghai Municipal Commission of Health and Family Planning [grant number 2017BR015]; Shanghai Technological Innovation Plan [grant number 18140902400].