McIlmoil S, Call G B, Barney M, Strickland J, Judd A M
Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT, 84602, USA; Neuroscience Center, Brigham Young University, Provo, UT, 84602, USA.
Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT, 84602, USA; Neuroscience Center, Brigham Young University, Provo, UT, 84602, USA.
Domest Anim Endocrinol. 2015 Oct;53:108-23. doi: 10.1016/j.domaniend.2015.05.006. Epub 2015 Jun 9.
Interleukin-6 (IL-6) is secreted by adrenocortical cells and modifies cortisol secretion. In this study, the effects of IL-6 on adrenal androgen release were investigated. The zona reticularis (ZR) was generally isolated from bovine adrenal glands by dissection. In select experiments, the intact adrenal cortex (ie, all 3 adrenocortical zones) was dissected from the adrenal glands. For androgen release experiments, ZR and intact adrenocortical cubes were dispersed into isolated cells, the cells cultured and exposed to IL-6 and/or adrenocorticotropic hormone (ACTH), and androgen release determined by radioimmunoassay. Basal and ACTH-stimulated androgen release from the ZR was inhibited by IL-6 in a concentration-dependent (10-1000 pg/mL) and time-dependent (4-24 h) manner (P < 0.01 by 1-way analysis of variance and the Bonferroni test). In contrast, IL-6 increased basal and ACTH-stimulated androgen release from mixed adrenocortical cells (P < 0.01). The mechanism of IL-6 inhibition of androgen release was investigated by exposing ZR strips to IL-6 and measuring the expression of the messenger RNA (mRNA) and protein of steroidogenic factors. Basal and ACTH-stimulated expression of the mRNA and protein for steroidogenic acute regulatory protein, cholesterol side chain cleavage enzyme, 3-β-hydroxysteroid dehydrogenase type 2, steroid 17-α-hydroxylase/17,20 lyase/17,20 desmolase, and the nuclear factor steroidogenic factor 1 (SF-1), that stimulates steroidogenesis, were decreased by IL-6 (P < 0.01). In contrast IL-6 increased the mRNA and protein for dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (DAX-1), a nuclear factor that inhibits steroidogenesis (P < 0.01). In summary, IL-6 decreased androgen release and the expression of steroidogenic factors in the ZR, and this decrease may be mediated in part through increasing DAX-1 and decreasing SF-1.
白细胞介素-6（IL-6）由肾上腺皮质细胞分泌并调节皮质醇分泌。在本研究中，对IL-6对肾上腺雄激素释放的影响进行了调查。网状带（ZR）通常通过解剖从牛肾上腺中分离出来。在特定实验中，从肾上腺中解剖出完整的肾上腺皮质（即所有3个肾上腺皮质带）。对于雄激素释放实验，将ZR和完整的肾上腺皮质小块分散成分离的细胞，培养细胞并使其暴露于IL-6和/或促肾上腺皮质激素（ACTH），然后通过放射免疫测定法测定雄激素释放。IL-6以浓度依赖性（10 - 1000 pg/mL）和时间依赖性（4 - 24小时）的方式抑制ZR的基础和ACTH刺激的雄激素释放（通过单因素方差分析和Bonferroni检验，P < 0.01）。相反，IL-6增加了混合肾上腺皮质细胞的基础和ACTH刺激的雄激素释放（P < 0.01）。通过将ZR条带暴露于IL-6并测量类固醇生成因子的信使核糖核酸（mRNA）和蛋白质的表达，研究了IL-6抑制雄激素释放的机制。IL-6降低了类固醇生成急性调节蛋白、胆固醇侧链裂解酶、2型3-β-羟基类固醇脱氢酶、类固醇17-α-羟化酶/17,20裂解酶/17,20脱氨酶以及刺激类固醇生成的核因子类固醇生成因子1（SF-1）的mRNA和蛋白质的基础和ACTH刺激的表达（P < 0.01）。相反，IL-6增加了剂量敏感性性反转、肾上腺发育不全关键区域、位于X染色体上的基因1（DAX-1）的mRNA和蛋白质，DAX-1是一种抑制类固醇生成的核因子（P < 0.01）。总之，IL-6降低了ZR中的雄激素释放和类固醇生成因子的表达，这种降低可能部分是通过增加DAX-1和降低SF-1介导的。
