Assessing the role of lactogenic hormones in human mammary gland development is limited due to issues accessing tissue samples and so development of a human in vitro three-dimensional mammosphere model with functions similar to secretory alveoli in the mammary gland can aid to overcome this shortfall. In this study, a mammosphere model has been characterised using human mammary epithelial cells grown on either mouse extracellular matrix or agarose and showed insulin is essential for formation of mammospheres. Insulin was shown to up-regulate extracellular matrix genes. Microarray analysis of these mammospheres revealed an up-regulation of differentiation, cell-cell junctions, and cytoskeleton organisation functions, suggesting mammosphere formation may be regulated through ILK signalling. Comparison of insulin and IGF-1 effects on mammosphere signalling showed that although IGF-1 could induce spherical structures, the cells did not polarise correctly as shown by the absence of up-regulation of polarisation genes and did not induce the expression of milk protein genes. This study demonstrated a major role for insulin in mammary acinar development for secretory differentiation and function indicating the potential for reduced lactational efficiency in women with obesity and gestational diabetes.

中文翻译：

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胰岛素调节人体乳腺发育和功能

由于获取组织样本的问题，评估催乳激素在人类乳腺发育中的作用受到限制，因此开发具有类似于乳腺分泌性肺泡功能的人类体外三维乳腺模型可以帮助克服这一不足。在这项研究中，使用在小鼠细胞外基质或琼脂糖上生长的人类乳腺上皮细胞表征了一个乳腺球模型，并表明胰岛素对于乳腺球的形成至关重要。胰岛素显示出上调细胞外基质基因。这些mammospheres 的微阵列分析揭示了分化、细胞-细胞连接和细胞骨架组织功能的上调，表明mammosphere 的形成可能通过ILK 信号传导进行调节。比较胰岛素和 IGF-1 对乳腺球信号传导的影响表明，虽然 IGF-1 可以诱导球形结构，但细胞没有正确极化，如缺乏极化基因上调所示，并且没有诱导乳蛋白基因的表达. 这项研究证明了胰岛素在乳腺腺泡发育中对分泌分化和功能的主要作用，表明肥胖和妊娠糖尿病女性的泌乳效率可能降低。