4.6 Review

Hormonal regulation of mammary gland development and lactation

Journal

NATURE REVIEWS ENDOCRINOLOGY
Volume -, Issue -, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41574-022-00742-y

Keywords

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Funding

  1. Family Larsson-Rosenquist Foundation
  2. Wellcome Trust Investigator Award [106995/Z/15/Z]
  3. National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Programme
  4. NIHR Senior Investigator Award [NF- SI-0514-10091]
  5. National Institutes of Health (NIH) [U01ES026140]
  6. Wellcome Trust [106995/Z/15/Z] Funding Source: Wellcome Trust

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Lactation is crucial for the health of both infants and mothers, and is regulated by reproductive and metabolic hormones. The development of mammary glands and synthesis of milk are closely related to hormonal functions, which are stimulated by infant suckling. After weaning, there is a large-scale cell loss in the glands leading to involution. The hormonal composition of human milk also has effects on infant health and development. Additionally, endocrine and metabolic diseases, labor interventions, and exposure to endocrine-disrupting chemicals can cause lactation insufficiency.
Lactation is critical to infant short-term and long-term health and protects mothers from breast cancer, ovarian cancer and type 2 diabetes mellitus. The mammary gland is a dynamic organ, regulated by the coordinated actions of reproductive and metabolic hormones. These hormones promote gland development from puberty onwards and induce the formation of a branched, epithelial, milk-secreting organ by the end of pregnancy. Progesterone withdrawal following placental delivery initiates lactation, which is maintained by increased pituitary secretion of prolactin and oxytocin, and stimulated by infant suckling. After weaning, local cytokine production and decreased prolactin secretion trigger large-scale mammary cell loss, leading to gland involution. Here, we review advances in the molecular endocrinology of mammary gland development and milk synthesis. We discuss the hormonal functions of the mammary gland, including parathyroid hormone-related peptide secretion that stimulates maternal calcium mobilization for milk synthesis. We also consider the hormonal composition of human milk and its associated effects on infant health and development. Finally, we highlight endocrine and metabolic diseases that cause lactation insufficiency, for example, monogenic disorders of prolactin and prolactin receptor mutations, maternal obesity and diabetes mellitus, interventions during labour and delivery, and exposure to endocrine-disrupting chemicals such as polyfluoroalkyl substances in consumer products and other oestrogenic compounds.

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