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Hormonal Regulation of the Immune Microenvironment in the Mammary Gland

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

It is well established that the development and homeostasis of the mammary gland are highly dependent upon the actions of ovarian hormones progesterone and estrogen, as well as the availability of prolactin for the pregnant and lactating gland. More recently it has become apparent that immune system cells and cytokines play essential roles in both mammary gland development as well as breast cancer. Here, we review hormonal effects on mammary gland biology during puberty, menstrual cycling, pregnancy, lactation and involution, and dissect how hormonal control of the immune system may contribute to mammary development at each stage via cytokine secretion and recruitment of macrophages, eosinophils, mast cells and lymphocytes. Collectively, these alterations may create an immunotolerant or inflammatory immune environment at specific developmental stages or phases of the menstrual cycle. Of particular interest for further research is investigation of the combinatorial actions of progesterone and estrogen during the luteal phase of the menstrual cycle and key developmental points where the immune system may play an active role both in mammary development as well as in the creation of an immunotolerant environment, thereby affecting breast cancer risk.

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Abbreviations

AR:

Androgen receptor

COX2:

Cyclooxygenase-2 enzyme

CSF:

Colony-stimulating factor

ERBB1/EGFR:

Epidermal growth factor receptor

ERα:

Estrogen receptor alpha

IFNG:

Interferon gamma

IL:

Interleukin

IκB:

Inhibitor of NF-κB

LPS:

Lipopolysaccharide

NF-κB:

Nuclear factor kappa B

PR:

Progesterone receptor

RANK:

Receptor activator of NF-κB

RANKL:

Receptor activator of NF-κB ligand

TDLU:

Terminal ductal lobular units

TEB:

Terminal end buds

Th:

Helper T lymphocytes

TLR:

Toll-like receptor

TNFA:

Tumor necrosis factor alpha

Treg:

Regulatory T lymphocytes

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Funding Support

EFN is supported by The Hospital Research Foundation Early Career Research Fellowship. WVI is a THRF Associate Professor and National Breast Cancer Foundation Early Career Fellow. PD is supported by an Australian Breast Cancer Research Postdoctoral Fellowship. We thank Mr Peter Adams for his expert illustrative assistance with the figures.

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Authors and Affiliations

  1. Discipline of Surgery, School of Medicine, The Queen Elizabeth Hospital, University of Adelaide, DX465702, 28 Woodville Road, Woodville, SA, 5011, Australia

    Eleanor F. Need, Vahid Atashgaran, Wendy V. Ingman & Pallave Dasari

  2. Robinson Research Institute, University of Adelaide, Adelaide, Australia

    Eleanor F. Need, Vahid Atashgaran, Wendy V. Ingman & Pallave Dasari

  3. School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia

    Wendy V. Ingman

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  1. Eleanor F. Need
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  2. Vahid Atashgaran
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  3. Wendy V. Ingman
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  4. Pallave Dasari
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Correspondence to Pallave Dasari.

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Need, E.F., Atashgaran, V., Ingman, W.V. et al. Hormonal Regulation of the Immune Microenvironment in the Mammary Gland. J Mammary Gland Biol Neoplasia 19, 229–239 (2014). https://doi.org/10.1007/s10911-014-9324-x

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  • DOI: https://doi.org/10.1007/s10911-014-9324-x

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