Investigation of the Role of the Mitogenic Neuropeptide Galanin in Mammary Gland Development and Carcinogenesis
Abstract
The neuropeptide galanin is involved in the control of a number of physiological functions including neuronal development and survival, neuroendocrine responses and mitogenesis. We report that null mutation of the galanin gene produced mice with reduced mammary ductal side branching during puberty and reduced lobuloalveolar development with lactation 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 interestingly 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, These studies provide evidence for an unexpected role of galanin in regulating prolactin phosphorylation and identify a novel regulatory mechanism where the modification state of prolactin induces different physiological effects in the mammary gland. 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. These data identify several novel functions of galanin during mammary gland development.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADB282300
Entities
People
- Christopher Ormandy
Organizations
- Garvan Institute of Medical Research