SFEBES2009 Poster Presentations Bone (25 abstracts)
Extra-pituitary expression of the prolactin gene in the bone and cartilage of an hPRL-Luc transgenic rat model
Sabrina Semprini 1 , Judith R McNeilly 2 , Lindsay Ramage 1 , David G Brownstein 3 , Donald M Salter 4 , Alan McNeilly 2 , Michael R H White 5 , Julian R E Davis 6 & John J Mullins 1
1Molecular Physiology, University of Edinburgh, Edinburgh, UK; 2MRC Human Reproductive Sciences Unit, University of Edinburgh, Edinburgh, UK; 3Research Animal Pathology Core, University of Edinburgh, Edinburgh, UK; 4Osteoarticular Research Group, University of Edinburgh, Edinburgh, UK; 5Centre for Cell Imaging, University of Liverpool, Liverpool, UK; 6Endocrine Sciences Research Group, University of Manchester, Manchester, UK.
Prolactin (PRL) is a peptide hormone produced by the anterior pituitary gland and it is commonly known for its lactogenic and mammotrophic effects. In humans and primates, prolactin is also expressed in extra-pituitary sites where it is associated with numerous biological functions, but its spectrum of expression varies in different species.
Hyperprolactinemia-induced osteoporosis is believed to be mediated by hypogonadism, but the expression of the prolactin receptor (PRLR) on osteoblasts suggests a direct effect of prolactin on bone remodelling. Very little is known about the expression of prolactin in chondrocytes and osteoblasts, and the possible autocrine/paracrine mode of action of PRL in these tissues. In order to study extra-pituitary human prolactin gene expression, we have generated a transgenic rat that expresses luciferase under the control of extensive regulatory regions of the human prolactin gene in the genomic context of a 166 kbp BAC construct. The rat has already proven to be ideal for in vivo imaging of the pituitary gland and of immune-related organs after intra-peritoneal injection of LPS (Semprini et al. 2009).
In vivo optical imaging of hPRL-Luc rats revealed luciferase signal in the ears, tail and paws, suggesting that the prolactin gene might be normally expressed in bone and cartilage. This was confirmed on human cartilage by rtPCR and immunohistochemistry, showing that the transgenic rat model faithfully reports sites of human prolactin expression, and that this extra-pituitary transgene expression was not merely an aberrant integration site effect. Immunohistochemistry of rat knee joints revealed luciferase protein and endogenous rat prolactin in cartilage from the growth plate and in osteoblasts of young rats. Prolactin, but not luciferase staining was also detected in rat osteocytes.
These observations indicate that prolactin is produced in bone and cartilage and might act locally in an autocrine/paracrine manner to regulate bone physiology.
Volume 21
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Endocrine Abstracts
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