title: Serotonin as a homeostatic regulator of lactation.
abstract: 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.
authors.affiliation: Department of Animal Sciences, University of Arizona, Tucson, AZ 85721, USA. rcollier@ag.arizona.edu
authors.forename: R J
authors.initials: RJ
authors.lastname: Collier
authors.forename: L L
authors.initials: LL
authors.lastname: Hernandez
authors.forename: N D
authors.initials: ND
authors.lastname: Horseman
mesh_terms: D000818:Animals; D002364:Caseins / Q000494:pharmacology; D002417:Cattle / Q000502:physiology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism; D025461:Feedback, Physiological; D005260:Female; D015870:Gene Expression; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007774:Lactation / Q000187:drug effects / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008892:Milk / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis; D011985:Receptors, Serotonin / Q000235:genetics / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
chemical_list: D002364:Caseins; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors