Transcriptomic changes underlying glucocorticoid-induced suppression of milk production by dairy cows.

Transcriptomic changes underlying glucocorticoid-induced suppression of milk production by dairy cows.
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糖皮质激素诱导的奶牛抑制糖皮质激素诱导的抑制作用的转录组变化。

DOI:
10.3389/fgene.2022.1072853
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发表时间:
2022
影响因子:
3.7
通讯作者:
--
中科院分区:
生物学3区
文献类型:
--
作者:

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奶牛的产奶量对糖皮质激素(GC)等应激激素水平的增加很敏感,GC也调节牛奶合成所需的几个基因的转录。虽然先前的研究发现,外源GC如地塞米松(DEX)会暂时抑制几个物种的产奶量,但对乳蛋白或乳脂率没有任何明显影响,但这种影响的机制尚未建立。在这项研究中,我们试图建立非怀孕奶牛在第二次哺乳(n=3-4;648-838 kg)单剂量外源地塞米松后乳腺内的变化。乳房的变化通过交替季度的连续活检进行监测,同时对牛奶产量和成分进行季度水平的监测。地塞米松可在12-36小时内提高血糖水平(p<0.05),在12-48小时内降低产奶量(p<0.05),在24小时内提高乳蛋白含量,瞬时降低乳糖和α-乳蛋白含量,但不改变乳脂水平。72小时后,牛奶产量的所有方面都恢复到处理前的水平。通过RNA测序和差异基因表达分析,确定了乳腺对DEX反应的转录变化。与产奶量和乳成分变化相一致的是,在注射地塞米松后12小时和24小时分别有519个和320个基因的差异表达(调整后p<0.05),所有基因的表达在72小时恢复到基线水平。在对地塞米松的响应转录变化中,乳糖合成途径中的元件在12小时显著下调,尤其是AQP3、GALE和LALBA(α-lactalrouble),而LALBA在24小时持续下调。这项工作支持了这样的假设,即对地塞米松的反应与由于乳腺上皮合成α-乳清蛋白和乳糖减少而同时抑制产奶量之间存在直接关系。糖皮质激素在应激状态下调节葡萄糖的顺应性需求的能力与免疫激活同时存在,这对奶牛和多种哺乳类动物都具有重要意义。
Milk production by dairy cows is sensitive to increased levels of stress hormones such as glucocorticoids (GC) that also regulate the transcription of several genes required for milk synthesis. Whereas previous studies identified that an exogenous GC such as dexamethasone (DEX) transiently suppresses milk yield in several species without any pronounced effect on milk protein or fat percentage, the mechanism underlying this effect has not been established. In this study we sought to establish changes within the mammary glands of non-pregnant dairy cows in their second lactation (n = 3–4; 648–838 kg) following a single dose of exogenous DEX. Changes in the udder were monitored by serial biopsy of alternating quarters, concurrent with quarter-level monitoring of milk yield and composition. Dexamethasone increased serum glucose levels from 12–36 h (p <0 .05), reduced milk yield from 12–48 h (p <0 .05), increased % milk protein content at 24 h post-DEX, and transiently decreased both milk lactose and α-lactalbumin content, while not altering the level of milk fat. After 72 h, all aspects of milk production had returned to pre-treatment levels. Transcriptomic changes in the mammary glands in response to DEX were identified by RNA sequencing followed by differential gene expression analysis. Coincident with the milk yield and composition changes was the differential expression of 519 and 320 genes at 12 and 24 h after DEX (adjusted p <0 .05), respectively, with the return of all gene expression to baseline levels by 72 h. Among the transcriptomic changes in response to DEX, there was notable downregulation of elements in the lactose synthesis pathway, specifically AQP3, GALE and LALBA (α-lactalbumin) at 12 h, and sustained downregulation of LALBA at 24 h. One gene in the pathway, UGP2, was upregulated at 12–24 h post-DEX. This work supports the hypothesis that there is a direct relationship between the response to DEX and the concurrent suppression of milk yield due to the reduced synthesis of α-lactalbumin and lactose by the mammary epithelium. The ability of glucocorticoids to modulate the homeorrhetic requirements for glucose during stressful states concurrent with immune activation bears significance for dairy animals as well as a broad range of lactating mammals.
DOI: 10.1093/nar/gkaa1113
发表时间: 2021-01-08
影响因子: 14.9
作者:
Gene Ontology Consortium
通讯作者: Gene Ontology Consortium
DOI: 10.5713/ajas.18.0108
发表时间: 2019-03-01
期刊: ASIAN-AUSTRALASIAN JOURNAL OF ANIMAL SCIENCES
影响因子: --
作者:
Hong, Heeok;Lee, Eunchae;Lee, Sang-Rak
通讯作者: Lee, Sang-Rak
DOI: 10.1042/bj0880213
发表时间: 1963-01-01
影响因子: 4.1
作者:
HARDWICK, DC;MEPHAM, TB;LINZELL, JL
通讯作者: LINZELL, JL
DOI: 10.3168/jds.s0022-0302(73)85275-0
发表时间: 1973-01-01
影响因子: 3.5
作者:
KRONFELD, DS;HARTMANN, PE
通讯作者: HARTMANN, PE
DOI: 10.1016/j.jsbmb.2009.02.007
发表时间: 2009-04
期刊: The Journal of steroid biochemistry and molecular biology
影响因子: --
作者:
Kerachian MA;Séguin C;Harvey EJ
通讯作者: Harvey EJ