Annibalini Giosuè, Agostini Deborah, Calcabrini Cinzia, Martinelli Chiara, Colombo Evelin, Guescini Michele, Tibollo Pasquale, Stocchi Vilberto, Sestili Piero
Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino Carlo Bo, Via I. Maggetti 26, 61029, Urbino, PU, Italy,
J Endocrinol Invest. 2014 Sep;37(9):861-9. doi: 10.1007/s40618-014-0118-1. Epub 2014 Jun 20.
Gender-related differences in sex hormones might have a key role in the development of atherosclerosis though direct vascular effects of sex hormones are not yet well understood. Thus, the main purpose of this study was to compare the effects of sex hormones on inflammatory response in Human Umbilical Vein Endothelial Cells (HUVECs) obtained from both male and female donors.
We analyzed the expression of receptors and enzymes relevant to the action of androgens (AR, 5α-reductase 1 and 5α-reductase 2) and estrogens (ERα, ERβ, and aromatase) in male and female HUVECs. Furthermore, we analyzed the effect of testosterone (T), 17β-estradiol (E2), dihydrotestosterone (DHT), and several androgenic-anabolic steroids (AAS) on VCAM-1, ICAM-1, and E-selectin gene expression and on adhesion of U937 cells to TNF-α-stimulated male and female HUVECs.
Our results reveal that in HUVECs, regardless of gender, the components involved in the androgen action pathway are predominant as compared to those of estrogen action pathway. In both HUVEC genders, the inflammatory effect of TNF-α was amplified by co-administration of T or DHT and several AAS frequently used in doping, while E2 had no effect.
This is the first study analyzing, under identical culture conditions, the key components of sex hormone response in male and female HUVECs and the possible role of sex hormones in regulating the endothelial inflammatory response. The data obtained in our experimental system showed a pro-inflammatory effect of androgens, while conclusively excluding any protective effect for all the tested hormones.
性激素方面的性别差异可能在动脉粥样硬化的发展中起关键作用，尽管性激素对血管的直接作用尚未完全明确。因此，本研究的主要目的是比较性激素对从男性和女性供体获取的人脐静脉内皮细胞（HUVECs）炎症反应的影响。
我们分析了雄性和雌性HUVECs中与雄激素（AR、5α - 还原酶1和5α - 还原酶2）及雌激素（ERα、ERβ和芳香化酶）作用相关的受体和酶的表达。此外，我们分析了睾酮（T）、17β - 雌二醇（E2）、双氢睾酮（DHT）以及几种雄激素 - 合成代谢类固醇（AAS）对VCAM - 1、ICAM - 1和E - 选择素基因表达以及U937细胞与TNF - α刺激的雄性和雌性HUVECs黏附的影响。
我们的结果显示，在HUVECs中，无论性别，与雌激素作用途径的成分相比，雄激素作用途径的成分占主导地位。在两种性别的HUVECs中，TNF - α的炎症作用通过同时给予T或DHT以及几种常用于兴奋剂的AAS而增强，而E2则无此作用。
这是第一项在相同培养条件下分析雄性和雌性HUVECs中性激素反应关键成分以及性激素在调节内皮炎症反应中可能作用的研究。我们实验系统中获得的数据显示雄激素具有促炎作用，同时明确排除了所有测试激素的任何保护作用。
