Epigenetic impact of hypothyroidism on the functional differentiation of the mammary gland in rats

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology Pub Date : 2024-05-09 DOI:10.1016/j.mce.2024.112267

Fiorella Campo Verde Arbocco , Lourdes Inés Pascual , Daiana García , Irina Ortiz , Carlos Gamarra-Luques , Rubén Walter Carón , María Belén Hapon

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引用次数: 0

Abstract

Mammary gland (MG) lactogenic differentiation involves epigenetic mechanisms. We have previously shown that hypothyroidism (HypoT) alters the MG transcriptome in lactation. However, the role of thyroid hormones (T3 and T4 a. k.a. THs) in epigenetic differentiation of MG is still unknown. We used a model of post-lactating HypoT rats to study in MG: a) Methylation and expression level of Gata3, Elf5, Stat6, Stat5a, Stat5b; b) Expression of Lalba, IL-4Rα and Ncoa1 mRNA; c) Histone H3 acetylation and d) Estrogen and progesterone concentration in serum. HypoT increases the estrogen serum level, decreases the progesterone level, promotes methylation of Stat5a, Stat5b and Stat6, decreasing their mRNA level and of its target genes (Lalba and IL-4Rα) and increases the Ncoa1 mRNA expression and histone H3 acetylation level. Our results proved that HypoT alters the post-lactation MG epigenome and could compromise mammary functional differentiation.

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甲状腺功能减退症对大鼠乳腺功能分化的表观遗传学影响

乳腺（MG）的泌乳分化涉及表观遗传机制。我们之前已经证明，甲状腺功能减退症（HypoT）会改变哺乳期乳腺的转录组。然而，甲状腺激素（T3和T4，又称THs）在MG表观遗传分化中的作用尚不清楚。我们利用泌乳后低TH大鼠模型研究了MG：a) Gata3、Elf5、Stat6、Stat5a、Stat5b的甲基化和表达水平；b) Lalba、IL-4Rα和Ncoa1 mRNA的表达；c) 组蛋白H3乙酰化；d) 血清中雌激素和孕酮的浓度。HypoT增加了血清中的雌激素水平，降低了孕酮水平，促进了Stat5a、Stat5b和Stat6的甲基化，降低了它们的mRNA水平及其靶基因（Lalba和IL-4Rα）的mRNA水平，增加了Ncoa1 mRNA的表达和组蛋白H3的乙酰化水平。我们的研究结果证明，HypoT改变了泌乳后MG表观基因组，并可能影响乳腺功能分化。

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来源期刊

Molecular and Cellular Endocrinology 医学-内分泌学与代谢

CiteScore

9.00

自引率

2.40%

发文量

174

审稿时长

42 days

期刊介绍： Molecular and Cellular Endocrinology was established in 1974 to meet the demand for integrated publication on all aspects related to the genetic and biochemical effects, synthesis and secretions of extracellular signals (hormones, neurotransmitters, etc.) and to the understanding of cellular regulatory mechanisms involved in hormonal control.