Progress 03/01/09 to 02/28/11
Outputs OUTPUTS: This project discovered key features of mammary gland physiology during lactation and involution. During this grant period two key findings moved this knowledge base forward dramatically. First, we discovered that enhancing intramammary serotonin activity by several means (drugs that target various aspects of serotonin metabolism) accelerates involution-like changes. This has led to the concept that these manipulations can be implemented practically as dry-off enhancers. We have successfully competed for SBIR funding (via formation of an outside company) to develop this commercially. Secondly, we have discovered that the intramammary serotonin system is a key regulator of calcium homeostasis during lactation. This regulatory system operates through specific mediators (PTHrP, Runx2, RANK-L, etc.). Future studies will be required to understand the full in vivo implications of these discoveries. PARTICIPANTS: Nelson D. Horseman, Ph.D. Principal Investigator Robert J. Collier, Ph.D. Co-Investigator Ekta Yadav, Research Assistant TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts Our project has opened an entirely new area of lactation biology. We have established that a monoamine (serotonin) regulates key aspects of lactation, including milk homeostasis and calcium homeostasis. These findings will have practical impacts on the dairy industry as they are implemented through specific drugs and other manipulations.
Publications
- 1: Pai VP, Horseman ND. Multiple cellular responses to serotonin contribute to epithelial homeostasis. PLoS One. 2011 Feb 24;6(2):e17028. PubMed PMID: 21390323; PubMed Central PMCID: PMC3044750.
- 2: Hernandez LL, Collier JL, Vomachka AJ, Collier RJ, Horseman ND. Suppression of lactation and acceleration of involution in the bovine mammary gland by a selective serotonin reuptake inhibitor. J Endocrinol. 2011 Apr;209(1):45-54. Epub 2011 Feb 9. PubMed PMID: 21307120.
- 3: Marshall AM, Nommsen-Rivers LA, Hernandez LL, Dewey KG, Chantry CJ, Gregerson KA, Horseman ND. Serotonin transport and metabolism in the mammary gland modulates secretory activation and involution. J Clin Endocrinol Metab. 2010 Feb;95(2):837-46. Epub 2009 Dec 4. PubMed PMID: 19965920; PubMed Central PMCID: PMC2840848.
- 4: Pai VP, Marshall AM, Hernandez LL, Buckley AR, Horseman ND. Altered serotonin physiology in human breast cancers favors paradoxical growth and cell survival. Breast Cancer Res. 2009;11(6):R81. Epub 2009 Nov 10. PubMed PMID: 19903352; PubMed Central PMCID: PMC2815543.
- 5: Hernandez LL, Limesand SW, Collier JL, Horseman ND, Collier RJ. The bovine mammary gland expresses multiple functional isoforms of serotonin receptors. J Endocrinol. 2009 Oct;203(1):123-31. Epub 2009 Aug 4. PubMed PMID: 19654143; PubMed Central PMCID: PMC2741409.
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