Department of Animal Science, Texas A&M University, College Station, Texas.
Department of Animal and Dairy Science, Mississippi State University, Starkville, Mississippi.
J Biochem Mol Toxicol. 2019 Jun;33(6):e22309. doi: 10.1002/jbt.22309. Epub 2019 Feb 24.
Glucocorticoids impair testosterone synthesis by an unknown mechanism. Stallions treated with the synthetic glucocorticoid dexamethasone had testes collected at 6 or 12 hours postinjection. The testicular expression of selected genes encoding nuclear receptors and steroidogenic enzymes was measured. At 6 hours, dexamethasone treatment decreased levels of NR0B2, NR4A1, NR5A1, and NR5A2 messenger RNAs (mRNAs) and NR5A2 mRNA levels remained depressed at 12 hours. In contrast, dexamethasone increased levels of NFKBIA mRNA at both time points. At 6 hours, dexamethasone did not alter levels of NR0B1, NR2F1, NR2F2, NR3C1, CYP11A1, CYP17A1, CYP19A1, DHCR24, GSTA3, HSD3B2, HSD17B3, LHCGR, or STAR mRNAs. In primary cultures of Leydig cells, 10 and 10 M dexamethasone decreased levels of NR4A1 and NR5A1 mRNAs and increased those of NFKBIA mRNA. Our discovery that dexamethasone downregulates NR4A1, NR5A1, and NR5A2 genes, known to be important for testicular functions, may be part of the mechanism by which glucocorticoids acutely decreases testosterone.
糖皮质激素通过未知机制损害睾酮的合成。接受合成糖皮质激素地塞米松治疗的种马在注射后 6 或 12 小时采集睾丸。测量了编码核受体和类固醇生成酶的选定基因的睾丸表达。在 6 小时时，地塞米松处理降低了 NR0B2、NR4A1、NR5A1 和 NR5A2 信使 RNA（mRNA）的水平，并且在 12 小时时 NR5A2 mRNA 的水平仍然降低。相比之下，地塞米松在两个时间点均增加了 NFKBIA mRNA 的水平。在 6 小时时，地塞米松未改变 NR0B1、NR2F1、NR2F2、NR3C1、CYP11A1、CYP17A1、CYP19A1、DHCR24、GSTA3、HSD3B2、HSD17B3、LHCGR 或 STAR mRNA 的水平。在睾丸间质细胞的原代培养中，10 和 10 M 地塞米松降低了 NR4A1 和 NR5A1 mRNA 的水平，并增加了 NFKBIA mRNA 的水平。我们发现地塞米松下调了 NR4A1、NR5A1 和 NR5A2 基因，这些基因对于睾丸功能很重要，这可能是糖皮质激素急性降低睾酮的机制的一部分。
