Investigation of the Role of the Mitogenic Neuropeptide Galanin in Mammary Gland Development and Carcinogenesis
Abstract
Null mutation of the galanin gene produced lactational failure following pregnancy. Galanin and galanin receptor 2 (GALR2) are expressed in the mammary gland and are differentially regulated during mammopoiesis. Mammary transplantation experiments demonstrated galanin does not act via autocrine or paracrine mechanisms in the mammary gland. Galanin knockout mice have decreased levels of secreted prolactin and were also found to have an increased ratio of phosphorylated to unmodified prolactin. Unmodified prolactin rescued the lactation failure and treatment of wildtype mice with a molecular mimic of phosphorylated prolactin inhibited lactation and alveolar differentiation. In addition treatment of whole mammary gland explants with galanin resulted in a 3.8 fold increase in the number of lobuloalveoli demonstrating that galanin also has a direct endocrine action on the mammary gland. Investigation of signalling mechanisms showed that galanin activated the Jak/Stat pathway while prolactin activated the Jak/Stat and MAPK pathways. Galanin was a potent inducer of milk protein gene expression. Transcript profiling revealed the synergist activity of galanin and prolactin. These data identify several novel functions of galanin during mammary gland.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADB285053
Entities
People
- Christopher J. Ormandy
Organizations
- United States Army Medical Research and Development Command