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

摘要

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.