Serotonin as a homeostatic regulator of lactation

• Published in: Domestic animal endocrinology 2012-08, Vol.43 (2), p.161-170
• Main Authors: Collier, R.J., Hernandez, L.L., Horseman, N.D.
• Format: Article
• Language: English
• Subjects: 5-hydroxytryptophan; Animals; blood vessels; Caseins - pharmacology; Cattle - physiology; Cells, Cultured; dairy cows; dairy protein; epithelial cells; Epithelial Cells - chemistry; Epithelial Cells - metabolism; Feedback, Physiological; Female; Gene Expression; Homeostasis - physiology; Humans; in situ hybridization; lactation; Lactation - drug effects; Lactation - physiology; Mammary gland; Mammary Glands, Animal - chemistry; Mammary Glands, Animal - metabolism; messenger RNA; Mice; milk; Milk - chemistry; milk secretion; milk synthesis; Milk yield; quantitative polymerase chain reaction; Receptor; Receptors, Serotonin - genetics; Receptors, Serotonin - physiology; reverse transcriptase polymerase chain reaction; RNA, Messenger - analysis; Serotonin; Serotonin - pharmacology; Serotonin - physiology; Serotonin Uptake Inhibitors - pharmacology; tight junctions; Transporter
• ISSN: 0739-7240; 1879-0054
• DOI: 10.1016/j.domaniend.2012.03.006

Serotonin (5-HT), a neurotransmitter produced in mammary epithelial cells (MECs), acts via autocrine–paracrine mechanisms on MECs to regulate milk secretion in a variety of species. Recent studies in dairy cows reported that 5-HT ligands affect milk yield and composition. We determined the mRNA expression of bovine 5-HT receptor (5-HTR) subtypes in bovine mammary tissue (BMT) and cultured bovine MECs. We then used pharmacologic agents to evaluate functional activities of 5-HTR subtypes. The mRNAs for five receptor isoforms (5-HTR1B, 5-HTR2A, 5-HTR2B, 5-HTR4, and 5-HTR7) were identified by conventional reverse transcription PCR, real-time PCR, and in situ hybridization in BMT. In addition to luminal MEC expression, 5-HTR4 was expressed in myoepithelium, and 5-HTR1B, HTR2A, and HTR2B were expressed in small mammary blood vessels. Studies to date report that there are multiple 5-HTR isoforms in mammary tissue of rodents, humans, and cattle. Inhibition of the 5-HT reuptake transporter with selective 5-HT reuptake inhibitors (SSRIs) disrupted tight junctions and decreased milk protein mRNA expression in mouse, human, and bovine mammary cells. Selective 5-HT reuptake inhibitors act to increase the cellular exposure to 5-HT by preventing reuptake of 5-HT by the cell and eventual degradation. Increasing 5-HT concentration in milk via inhibiting its reuptake (SSRI), or by increasing the precursor for 5-HT synthesis 5-hydroxytryptophan, accelerated decline in milk synthesis at dry-off. We conclude that the 5-HT system in mammary tissue acts as a homeostatic regulator of lactation.