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Insulin, a key regulator of hormone responsive milk protein synthesis during lactogenesis in murine mammary explants

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Abstract

Murine milk protein gene expression requires insulin, hydrocortisone, and prolactin; however, the role of insulin is not well understood. This study, therefore, examined the requirement of insulin for milk protein synthesis. Mammary explants were cultured in various combinations of the lactogenic hormones and global changes in gene expression analysed using Affymetrix microarray. The expression of 164 genes was responsive to insulin, and 18 were involved in protein synthesis at the level of transcription and posttranscription, as well as amino acid uptake and metabolism. The folate receptor gene was increased by fivefold, highlighting a potentially important role for the hormone in folate metabolism, a process that is emerging to be central for protein synthesis. Interestingly, gene expression of two milk protein transcription factors, Stat5a and Elf5, previously identified as key components of prolactin signalling, both showed an essential requirement for insulin. Subsequent experiments in HCll cells confirmed that Stat5a and Elf5 gene expression could be induced in the absence of prolactin but in the presence of insulin. Whereas prolactin plays an essential role in phosphorylating and activating Stat5a, gene expression is only induced when insulin is present. This indicates insulin plays a crucial role in the transcription of the milk protein genes.

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Acknowledgements

This work was supported by Dairy Australia and the Co-operative Research Centre for Innovative Dairy Products.

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Authors and Affiliations

  1. CRC for Innovative Dairy Products, Department of Zoology, University of Melbourne, Melbourne, VIC, 3010, Australia

    Karensa K. Menzies, Christophe Lefèvre & Kevin R. Nicholas

  2. Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia

    Heather J. Lee & Christopher J. Ormandy

  3. Victorian Bioinformatics Consortium, Monash University, Clayton, VIC, 3080, Australia

    Christophe Lefèvre

  4. School of Veterinary Science, University of Melbourne, Werribee, VIC, 3030, Australia

    Keith L. Macmillan

  5. Institute of Technology Research and Innovation, Deakin University, Geelong, 3217, Australia

    Karensa K. Menzies, Christophe Lefèvre & Kevin R. Nicholas

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  1. Karensa K. Menzies
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  2. Heather J. Lee
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  3. Christophe Lefèvre
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Correspondence to Karensa K. Menzies.

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ESM Table 1

Key genes involved in lactation that are differentially expressed in murine mammary explants cultured with IFP. (DOC 98 kb)

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Menzies, K.K., Lee, H.J., Lefèvre, C. et al. Insulin, a key regulator of hormone responsive milk protein synthesis during lactogenesis in murine mammary explants. Funct Integr Genomics 10, 87–95 (2010). https://doi.org/10.1007/s10142-009-0140-0

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