Serotonin transport and metabolism in the mammary gland modulates secretory activation and involution

J Clin Endocrinol Metab. 2010 Feb;95(2):837-46. doi: 10.1210/jc.2009-1575. Epub 2009 Dec 4.


Context: Serotonin [5-hydroxytryptamine (5-HT)] is an important local regulator of lactation homeostasis; however, the roles for the serotonin reuptake transporter and monoamine oxidase have not been known.

Objective: The aim of the study was to determine whether drugs that impact 5-HT affect human lactation physiology.

Design and setting: We conducted laboratory studies of human and animal models and an observational study of the onset of copious milk secretion in postpartum women at a university medical center.

Participants: We studied women expecting their first live-born infant; exclusion criteria were: referred to the medical center for another medical condition, known contraindication to breastfeed, and less than 19 yr of age and unable to obtain parental consent.

Intervention(s): The mothers were interviewed. The cell and animal studies consisted of a variety of biochemical, pharmacological, and genetic interventions.

Main outcome measure(s): The human subjects outcome was prevalence of delayed onset of copious milk secretion. The cell and animal outcomes were physiological and morphological.

Results: Inhibiting serotonin reuptake in mammary epithelial cells altered barrier function, and the effects were amplified by coadministering a monoamine oxidase inhibitor. Direct delivery of fluoxetine by slow-release pellets caused localized involution. TPH1 knockout mice displayed precocious secretory activation. Among a cohort of 431 women, those taking SSRI were more likely (P = 0.02) to experience delayed secretory activation.

Conclusions: Medications that perturb serotonin balance dysregulate lactation, and the effects are consistent with those predicted by the physiological effects of intramammary 5-HT bioactivity. Mothers taking serotonergic drugs may need additional support to achieve their breastfeeding goals.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Breast / metabolism*
  • Cells, Cultured
  • Electric Impedance
  • Female
  • Fluoxetine / pharmacology
  • Humans
  • Lactation*
  • Mammary Glands, Animal / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Monoamine Oxidase / physiology
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Serotonin / metabolism*
  • Serotonin Plasma Membrane Transport Proteins / analysis
  • Serotonin Plasma Membrane Transport Proteins / physiology
  • Tryptophan Hydroxylase / physiology


  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Serotonin
  • Tph1 protein, mouse
  • Tryptophan Hydroxylase
  • Monoamine Oxidase