Bomfim G F, Merighe G K F, de Oliveira S A, Negrao J A
Department of Basic Sciences, Faculty of Animal Science and Food Engineering (FZEA), University of Sao Paulo (USP), Pirassununga, SP, 13635-900 Brazil.
Department of Basic Sciences, Faculty of Animal Science and Food Engineering (FZEA), University of Sao Paulo (USP), Pirassununga, SP, 13635-900 Brazil.
J Dairy Sci. 2022 Jan;105(1):818-830. doi: 10.3168/jds.2021-20364. Epub 2021 Oct 28.
Cortisol (CORT) induces mammary development in late gestation and is fundamental to the differentiation of mammary epithelial cells and lactogenesis. The objective of this study was to investigate the relationship between CORT, insulin, prolactin, growth hormone, and insulin-like growth factor-1 in milk as well as the effect of CORT on the expression of receptors of insulin (INSR), prolactin (PRLR), growth hormone (GHR); we also studied the insulin-like growth factor-1 (IGF1R), glucocorticoid (NR3C1), mineralocorticoid (NR3C2), B-cell lymphoma 2 (BCL2), BCL-2-like protein X (BAX) genes, and the apoptosis rate of mammary epithelial cells of lactating Saanen goats in vivo and in vitro. The following experiments were conducted: (1) comparing hormone release in milk and blood after ACTH or a placebo administration; (2) evaluating the effect of acute CORT increases in mammary gland expression and milk yield in vivo; and (3) evaluating the effect of a chronic increase in CORT concentration in epithelial mammary cell apoptosis in vitro. In vivo, ACTH administration significantly increased CORT release but did not affect insulin, prolactin, growth hormone, and insulin-like growth factor-1 release in plasma and milk versus placebo. The results show also that a low CORT release after ACTH administration increased the expression of GHR and PRLR genes in the mammary tissue. Indeed, CORT release significantly increased the milk yield from goats subjected to ACTH versus goats subjected to the placebo. However, a higher amount of CORT added in vitro upregulated the NR3C1, GHR, PRLR, and BAX genes and downregulated the IGF1R and INSR genes, which could negatively modulate the apoptosis of mammary epithelial cells. Finally, the effect of CORT in vivo after ACTH administration demonstrated the increased expression of the PRLR and GHR genes, which may improve epithelial cell responsiveness and be associated with the positive effect of CORT observed on milk yield at mid-end lactation.
皮质醇（CORT）在妊娠后期诱导乳腺发育，对乳腺上皮细胞分化和泌乳至关重要。本研究的目的是探讨牛奶中CORT、胰岛素、催乳素、生长激素和胰岛素样生长因子-1之间的关系，以及CORT对胰岛素受体（INSR）、催乳素受体（PRLR）、生长激素受体（GHR）；胰岛素样生长因子-1受体（IGF1R）、糖皮质激素受体（NR3C1）、盐皮质激素受体（NR3C2）、B细胞淋巴瘤2（BCL2）、BCL-2样蛋白X（BAX）基因表达的影响，以及对泌乳期萨能山羊乳腺上皮细胞凋亡率的影响。进行了以下实验：（1）比较促肾上腺皮质激素（ACTH）或安慰剂给药后牛奶和血液中的激素释放；（2）评估急性CORT增加对体内乳腺表达和产奶量的影响；（3）评估慢性增加CORT浓度对体外乳腺上皮细胞凋亡的影响。在体内，与安慰剂相比，给予ACTH显著增加了CORT释放，但不影响血浆和牛奶中胰岛素、催乳素、生长激素和胰岛素样生长因子-1的释放。结果还表明，ACTH给药后低CORT释放增加了乳腺组织中GHR和PRLR基因的表达。事实上，与接受安慰剂的山羊相比，接受ACTH的山羊CORT释放显著增加了产奶量。然而，体外添加较高量的CORT上调了NR3C1、GHR、PRLR和BAX基因，下调了IGF1R和INSR基因，这可能对乳腺上皮细胞凋亡产生负调节作用。最后，ACTH给药后CORT在体内的作用表明PRLR和GHR基因表达增加，这可能改善上皮细胞反应性，并与泌乳中期至末期观察到的CORT对产奶量的积极作用相关。
