Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
Department of Experimental Oncology, IEO European Institute of Oncology IRCCS, Milan, Italy.
J Steroid Biochem Mol Biol. 2020 Oct;203:105732. doi: 10.1016/j.jsbmb.2020.105732. Epub 2020 Aug 7.
Gastrointestinal function is known to be regulated by steroid molecules produced by the gonads, the adrenal glands and the gut microbiota. However, we have a limited knowledge on the functional significance of local steroid production by gastrointestinal tract tissue. On this basis, we have here evaluated, as a first methodological approach, the expression of steroidogenic molecules and the local levels of key steroids in the male rat colon. Our findings indicate that the colon tissue expresses molecules involved in the early steps of steroidogenesis and in the consecutive synthesis and metabolism of steroid hormones, such as progesterone, testosterone and 17β-estradiol. In addition, the levels of the steroid hormone precursor pregnenolone and the levels of active metabolites of progesterone and testosterone, such as dihydroprogesterone, tetrahydroprogesterone, dihydrotestosterone and 17β-estradiol, were higher in colon than in plasma. Higher levels of the androgen metabolite 3α-diol were detected in the colon in comparison with another non-classical steroidogenic tissue, such as the cerebral cortex. These findings suggest the existence of local steroid synthesis and metabolism in the colon, with the production of active steroid metabolites that may impact on the activity of the enteric nervous system and on the composition of the gut microbiota.
胃肠道功能被认为受性腺、肾上腺和肠道微生物群产生的甾体分子调节。然而，我们对胃肠道组织局部甾体生成的功能意义知之甚少。在此基础上，我们作为一种初步的方法学方法，评估了雄性大鼠结肠中甾体生成分子的表达和关键甾体的局部水平。我们的研究结果表明，结肠组织表达了参与甾体生成早期步骤以及甾体激素（如孕酮、睾丸素和 17β-雌二醇）的连续合成和代谢的分子。此外，甾体激素前体孕烯醇酮的水平和孕酮和睾丸素的活性代谢物，如二氢孕酮、四氢孕酮、二氢睾丸素和 17β-雌二醇的水平在结肠中高于血浆。与另一种非经典甾体生成组织如大脑皮层相比，在结肠中检测到更高水平的雄激素代谢物 3α-二醇。这些发现表明在结肠中存在局部甾体合成和代谢，产生的活性甾体代谢物可能影响肠神经系统的活性和肠道微生物群的组成。
