Serotonin Transport and Metabolism in the Mammary Gland Modulates Secretory Activation and Involution

Abstract

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. The aim of the study was to determine whether drugs that impact 5-HT affect human lactation physiology. 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. 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. The mothers were interviewed. The cell and animal studies consisted of a variety of biochemical, pharmacological, and genetic interventions. The human subjects outcome was prevalence of delayed onset of copious milk secretion. The cell and animal outcomes were physiological and morphological. 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. 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.